Loss of synapse and functional connectivity in brain circuits is associated with aging and neurodegeneration,however,few molecular mechanisms are known to intrinsically promote synaptogenesis or enhance synapse functi...Loss of synapse and functional connectivity in brain circuits is associated with aging and neurodegeneration,however,few molecular mechanisms are known to intrinsically promote synaptogenesis or enhance synapse function.We have previously shown that MET receptor tyrosine kinase in the developing cortical circuits promotes dendritic growth and dendritic spine morphogenesis.To investigate whether enhancing MET in adult cortex has synapse regenerating potential,we created a knockin mouse line,in which the human MET gene expression and signaling can be turned on in adult(10–12 months)cortical neurons through doxycycline-containing chow.We found that similar to the developing brain,turning on MET signaling in the adult cortex activates small GTPases and increases spine density in prefrontal projection neurons.These findings are further corroborated by increased synaptic activity and transient generation of immature silent synapses.Prolonged MET signaling resulted in an increasedα-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid/N-methyl-Daspartate(AMPA/NMDA)receptor current ratio,indicative of enhanced synaptic function and connectivity.Our data reveal that enhancing MET signaling could be an interventional approach to promote synaptogenesis and preserve functional connectivity in the adult brain.These findings may have implications for regenerative therapy in aging and neurodegeneration conditions.展开更多
Transforming growth factor-beta 1(TGF-β1)has been extensively studied for its pleiotropic effects on central nervous system diseases.The neuroprotective or neurotoxic effects of TGF-β1 in specific brain areas may de...Transforming growth factor-beta 1(TGF-β1)has been extensively studied for its pleiotropic effects on central nervous system diseases.The neuroprotective or neurotoxic effects of TGF-β1 in specific brain areas may depend on the pathological process and cell types involved.Voltage-gated sodium channels(VGSCs)are essential ion channels for the generation of action potentials in neurons,and are involved in various neuroexcitation-related diseases.However,the effects of TGF-β1 on the functional properties of VGSCs and firing properties in cortical neurons remain unclear.In this study,we investigated the effects of TGF-β1 on VGSC function and firing properties in primary cortical neurons from mice.We found that TGF-β1 increased VGSC current density in a dose-and time-dependent manner,which was attributable to the upregulation of Nav1.3 expression.Increased VGSC current density and Nav1.3 expression were significantly abolished by preincubation with inhibitors of mitogen-activated protein kinase kinase(PD98059),p38 mitogen-activated protein kinase(SB203580),and Jun NH2-terminal kinase 1/2 inhibitor(SP600125).Interestingly,TGF-β1 significantly increased the firing threshold of action potentials but did not change their firing rate in cortical neurons.These findings suggest that TGF-β1 can increase Nav1.3 expression through activation of the ERK1/2-JNK-MAPK pathway,which leads to a decrease in the firing threshold of action potentials in cortical neurons under pathological conditions.Thus,this contributes to the occurrence and progression of neuroexcitatory-related diseases of the central nervous system.展开更多
BACKGROUND The induced-membrane technique was initially described by Masquelet as an effective treatment for large bone defects,especially those caused by infection.Here,we report a case of chronic osteomyelitis of th...BACKGROUND The induced-membrane technique was initially described by Masquelet as an effective treatment for large bone defects,especially those caused by infection.Here,we report a case of chronic osteomyelitis of the radius associated with a 9 cm bone defect,which was filled with a large allogeneic cortical bone graft from a bone bank.Complete bony union was achieved after 14 months of follow-up.Previous studies have used autogenous bone as the primary bone source for the Masquelet technique;in our case,the exclusive use of allografts is as successful as the use of autologous bone grafts.With the advent of bone banks,it is possible to obtain an unlimited amount of allograft,and the Masquelet technique may be further improved based on this new way of bone grafting.CASE SUMMARY In this study,we reported a case of repair of a long bone defect in a 40-year-old male patient,which was characterized by the utilization of allograft cortical bone combined with the Masquelet technique for the treatment of the patient's long bone defect in the forearm.The patient's results of functional recovery of the forearm were surprising,which further deepens the scope of application of Masquelet technique and helps to strengthen the efficacy of Masquelet technique in the treatment of long bones indeed.CONCLUSION Allograft cortical bone combined with the Masquelet technique provides a new method of treatment to large bone defect.展开更多
Objective: To study the relationship between cortical auditory evoked potential (CAEP) thresholds and behavioral thresholds in pediatric populations with sensorineural hearing loss (SNHL). Methods: Fifteen children (m...Objective: To study the relationship between cortical auditory evoked potential (CAEP) thresholds and behavioral thresholds in pediatric populations with sensorineural hearing loss (SNHL). Methods: Fifteen children (mean age 6.8 years) with bilateral SNHL underwent behavioral pure-tone audiometry and CAEP testing at 0.5, 1, 2, and 4 kHz. CAEP thresholds were determined using tone bursts, and correlations between CAEP and pure-tone thresholds were analyzed using Pearson correlation and t-tests. Results: A strong positive correlation was observed between P1 thresholds and behavioral thresholds across all test frequencies: 0.5 kHz (r = 0.765, p Conclusion: The strong correlation between P1 and behavioral thresholds demonstrates the reliability of CAEP testing for estimating auditory thresholds in children. These findings support the use of CAEP testing as a reliable objective tool for threshold estimation, particularly in cases where behavioral responses cannot be reliably obtained. When adjusted with frequency-specific correction values, CAEP testing provides a reliable method for assessing hearing thresholds in pediatric populations.展开更多
After stroke,even high-functioning individuals may experience compromised bimanual coordination and fine motor dexterity,leading to reduced functional independence.Bilateral arm training has been proposed as a promisi...After stroke,even high-functioning individuals may experience compromised bimanual coordination and fine motor dexterity,leading to reduced functional independence.Bilateral arm training has been proposed as a promising intervention to address these deficits.However,the neural basis of the impairment of functional fine motor skills and their relationship to bimanual coordination performance in stroke patients remains unclear,limiting the development of more targeted interventions.To address this gap,our study employed functional near-infrared spectroscopy to investigate cortical responses in patients after stroke as they perform functional tasks that engage fine motor control and coordination.Twenty-four high-functioning patients with ischemic stroke(7 women,17 men;mean age 64.75±10.84 years)participated in this cross-sectional observational study and completed four subtasks from the Purdue Pegboard Test,which measures unimanual and bimanual finger and hand dexterity.We found significant bilateral activation of the sensorimotor cortices during all Purdue Pegboard Test subtasks,with bimanual tasks inducing higher cortical activation than the assembly subtask.Importantly,patients with better bimanual coordination exhibited lower cortical activation during the other three Purdue Pegboard Test subtasks.Notably,the observed neural response patterns varied depending on the specific subtask.In the unaffected hand task,the differences were primarily observed in the ipsilesional hemisphere.In contrast,the bilateral sensorimotor cortices and the contralesional hemisphere played a more prominent role in the bimanual task and assembly task,respectively.While significant correlations were found between cortical activation and unimanual tasks,no significant correlations were observed with bimanual tasks.This study provides insights into the neural basis of bimanual coordination and fine motor skills in high-functioning patients after stroke,highlighting task-dependent neural responses.The findings also suggest that patients who exhibit better bimanual performance demonstrate more efficient cortical activation.Therefore,incorporating bilateral arm training in post-stroke rehabilitation is important for better outcomes.The combination of functional near-infrared spectroscopy with functional motor paradigms is valuable for assessing skills and developing targeted interventions in stroke rehabilitation.展开更多
Cortical electrodes are a powerful tool for the stimulation and/or recording of electrical activity in the nervous system.However,the inevitable wound caused by surgical implantation of electrodes presents bacterial i...Cortical electrodes are a powerful tool for the stimulation and/or recording of electrical activity in the nervous system.However,the inevitable wound caused by surgical implantation of electrodes presents bacterial infection and inflammatory reaction risks associated with foreign body exposure.Moreover,inflammation of the wound area can dramatically worsen in response to bacterial infection.These consequences can not only lead to the failure of cortical electrode implantation but also threaten the lives of patients.Herein,we prepared a hydrogel made of bacterial cellulose(BC),a flexible substrate for cortical electrodes,and further loaded antibiotic tetracycline(TC)and the anti-inflammatory drug dexamethasone(DEX)onto it.The encapsulated drugs can be released from the BC hydrogel and effectively inhibit the growth of Gram-negative and Gram-positive bacteria.Next,therapeutic cortical electrodes were developed by integrating the drug-loaded BC hydrogel and nine-channel serpentine arrays;these were used to record electrocorticography(ECoG)signals in a rat model.Due to the controlled release of TC and DEX from the BC hydrogel substrate,therapeutic cortical electrodes can alleviate or prevent symptoms associated with the bacterial infection and inflammation of brain tissue.This approach facilitates the development of drug delivery electrodes for resolving complications caused by implantable electrodes.展开更多
As three-dimensional“organ-like”aggregates,human cortical organoids have emerged as powerful models for studying human brain evolution and brain disorders with unique advantages of humanspecificity,fidelity and mani...As three-dimensional“organ-like”aggregates,human cortical organoids have emerged as powerful models for studying human brain evolution and brain disorders with unique advantages of humanspecificity,fidelity and manipulation.Human cortical organoids derived from human pluripotent stem cells can elaborately replicate many of the key properties of human cortical development at the molecular,cellular,structural,and functional levels,including the anatomy,functional neural network,and interaction among different brain regions,thus facilitating the discovery of brain development and evolution.In addition to studying the neuro-electrophysiological features of brain cortex development,human cortical organoids have been widely used to mimic the pathophysiological features of cortical-related disease,especially in mimicking malformations of cortical development,thus revealing pathological mechanism and identifying effective drugs.In this review,we provide an overview of the generation of human cortical organoids and the properties of recapitulated cortical development and further outline their applications in modeling malformations of cortical development including pathological phenotype,underlying mechanisms and rescue strategies.展开更多
Bone is a multi-phase,non-homogeneous material that exhibits strain rate sensitivity,and it may fail under compression,tension,torsion,or a combination of these loading.The mechanical properties of cortical bone with ...Bone is a multi-phase,non-homogeneous material that exhibits strain rate sensitivity,and it may fail under compression,tension,torsion,or a combination of these loading.The mechanical properties of cortical bone with strain rate effect under compression and tension have been obtained through the application of the split Hopkinson pressure/tension bar technique,but no such studies have been reported for determining the strain rate behavior properties of bony materials under torsion.In this study,the shear stress-strain curves with the rate-dependent cortical bone subjected to dynamic torsional loading were first obtained using a torsional split Hopkinson bar system.Based on the experiments,an improved mathematical model consisting of elastic,viscoelastic,and viscoplastic components was used to identify the material parameters of the cortical bone.Detailed material properties are derived through constitutive relations.The results may assist researchers in developing more accurate models of cortical bone behavior under different load conditions.展开更多
Background: We present a compelling case fitting the phenomenon of cortical spreading depression detected by intraoperative neurophysiological monitoring (IONM) following an intraoperative seizure during a craniotomy ...Background: We present a compelling case fitting the phenomenon of cortical spreading depression detected by intraoperative neurophysiological monitoring (IONM) following an intraoperative seizure during a craniotomy for revascularization. Cortical spreading depression (CSD, also called cortical spreading depolarization) is a pathophysiological phenomenon whereby a wave of depolarization is thought to propagate across the cerebral cortex, creating a brief period of relative neuronal inactivity. The relationship between CSD and seizures is unclear, although some literature has made a correlation between seizures and a cortical environment conducive to CSD. Methods: Intraoperative somatosensory evoked potentials (SSEPs) and electroencephalography (EEG) were monitored continuously during the craniotomy procedure utilizing standard montages. Electrophysiological data from pre-ictal, ictal, and post-ictal periods were recorded. Results: During the procedure, intraoperative EEG captured a generalized seizure followed by a stepwise decrease in somatosensory evoked potential cortical amplitudes, compelling for the phenomenon of CSD. The subsequent partial recovery of neuronal function was also captured electrophysiologically. Discussion: While CSD is considered controversial in some aspects, intraoperative neurophysiological monitoring allowed for the unique analysis of a case demonstrating a CSD-like phenomenon. To our knowledge, this is the first published example of this phenomenon in which intraoperative neurophysiological monitoring captured a seizure, along with a stepwise subsequent reduction in SSEP cortical amplitudes not explained by other variables.展开更多
Aim: To study the effects of rhynchophylline (Rhy) on the L type calcium channels in freshly dissociated cortical neurons of Wistar rats during acute hypoxia. Methods: Cell attached configuration of patch clamp tech...Aim: To study the effects of rhynchophylline (Rhy) on the L type calcium channels in freshly dissociated cortical neurons of Wistar rats during acute hypoxia. Methods: Cell attached configuration of patch clamp technique. L type calcium channel was activated by stepping from 40 mV to 0 mV. Results: The results showed that the L type calcium channels of cortical neurons were activated by acute hypoxia. The mean open time of the channel was increased, the mean close time decreased and the open state probability raised during acute hypoxia. Rhy (15 and 30μmol·L -1 ) in concentration dependent manner blocked activity of the channels. The drug shortened the mean open time of the channels from 8 87 ms to 3 03 ms and 2 23 ms ( P 【0 001), prolonged the mean close time from 9 23 ms to 38 84 ms and 54 43 ms ( P 【0 001), and decreased the open state probability from 0 142 to 0 031 and 0 025 ( P 【0 001) under the hypoxia condition, respectively. The effects of Rhy were similar to but weaker than those of verapamil (15 μmol·L -1 ). Conclusion: The study confirmed that Rhy has the blockade effects on L type calcium channels in cortical neurons of rats during hypoxia, by which it protects the brain from hypoxic injury.展开更多
Psychophysical studies suggest that lateral extrastriate visual cortical areas in cats may mediate the sparing of vision largely by network reorganization following lesions of early visual cortical areas. To date, how...Psychophysical studies suggest that lateral extrastriate visual cortical areas in cats may mediate the sparing of vision largely by network reorganization following lesions of early visual cortical areas. To date, however, there is little direct physiological evidence to support this hypothesis. Using in vivo single-anit recording techniques, we examined the response of neurons in areas 19, 21, and 20 to different types of visual stimulation in cats with or without acute bilateral lesions in areas 17 and 18. Our results showed that, relative to the controls, acute lesions inactivated the response of 99.3% of neurons to moving gratings and 93% of neurons to flickering square stimuli＇in areas 19, 21, and 20. These results indicated that acute lesions of primary visual areas in adult eats may impair most visual abilities. Sparing of vision in cats with neonatal lesions in early visual cortical areas may result largely from a postoperative reorganization of visual pathways from subcortical nucleus to extrastriate visual cortical areas.展开更多
With the development of neuroscience, substantial advances have been achieved in peripheral nerve regeneration over the past decades. However, peripheral nerve injury remains a critical public health problem because o...With the development of neuroscience, substantial advances have been achieved in peripheral nerve regeneration over the past decades. However, peripheral nerve injury remains a critical public health problem because of the subsequent impairment or absence of sensorimotor function. Uncomfortable complications of peripheral nerve injury, such as chronic pain, can also cause problems for families and society. A number of studies have demonstrated that the proper functioning of the nervous system depends not only on a complete connection from the central nervous system to the surrounding targets at an anatomical level, but also on the continuous bilateral communication between the two. After peripheral nerve injury, the interruption of afferent and efferent signals can cause complex pathophysiological changes, including neurochemical alterations, modifications in the adaptability of excitatory and inhibitory neurons, and the reorganization of somatosensory and motor regions. This review discusses the close relationship between the cerebral cortex and peripheral nerves. We also focus on common therapies for peripheral nerve injury and summarize their potential mechanisms in relation to cortical plasticity. It has been suggested that cortical plasticity may be important for improving functional recovery after peripheral nerve damage. Further understanding of the potential common mechanisms between cortical reorganization and nerve injury will help to elucidate the pathophysiological processes of nerve injury, and may allow for the reduction of adverse consequences during peripheral nerve injury recovery. We also review the role that regulating reorganization mechanisms plays in functional recovery, and conclude with a suggestion to target cortical plasticity along with therapeutic interventions to promote peripheral nerve injury recovery.展开更多
Objective To investigate the cytotoxic mechanism of cadmium（Cd） on cerebral cortical neurons.Methods The primary cultures of rat cerebral cortical neurons were treated with different concentrations of cadmium acetat...Objective To investigate the cytotoxic mechanism of cadmium（Cd） on cerebral cortical neurons.Methods The primary cultures of rat cerebral cortical neurons were treated with different concentrations of cadmium acetate（0,5,10,and 20 μmol/L）,and then the cell viability,apoptosis,ultrastructure,intracellular [Ca2＋]i and reactive oxygen species（ROS） levels,mitochondrial membrane potential（ΔΨ）,activities of catalase（CAT） and superoxide dismutase（SOD） were measured.Results A progressive loss in cell viability and an increased number of apoptotic cells were observed.In addition,Cd-induced apoptotic morphological changes in cerebral cortical neurons were also demonstrated by Hoechst 33258 staining.Meanwhile,ultrastructural changes were distortion of mitochondrial cristae and an unusual arrangement.Simultaneously,elevation of intracellular [Ca2＋]i and ROS levels,depletion of ΔΨ were revealed in a dose-dependent manner during the exposure.Moreover,CAT and SOD activities in the living cells increased significantly.Conclusion Exposure of cortical neurons to different doses of Cd led to cellular death,mediated by an apoptotic mechanism,and the apoptotic death induced by oxidative stress may be a potential reason.And the disorder of intracellular homeostasis caused by oxidative stress and mitochondrial dysfunction may be a trigger for apoptosis in cortical neurons.展开更多
The coexistence of myelolipoma within adrenal cortical adenoma is extremely rare,for both tumors present usually as separate entities.There are only 16 such cases reported worldwide.To the best of our knowledge,the ca...The coexistence of myelolipoma within adrenal cortical adenoma is extremely rare,for both tumors present usually as separate entities.There are only 16 such cases reported worldwide.To the best of our knowledge,the case we reported here is the first one of myxoid adrenal cortical adenoma associated with myelolipoma reported.A 32-year-old Chinese woman with 4-year history of hypertension was presented in our study.Computed tomography(CT)of the abdomen showed a large heterogene- ously-enhancing mass(4.5 cm in diameter)in the left suprarenal region.Clinical history and laboratory results suggest a metabolic disorder as Conn's syndrome.The patient underwent a left adrenalectomy,and a histopathological study confirmed the mass to be a myxoid adrenal cortical adenoma containing myelolipoma.The patient was postoperatively well and discharged uneventfully.In the present case report,we also discuss the etiology of simultaneous myelolipoma and adrenal adenoma associated with Conn's syndrome,and the methods of the diagnosis and differential diagnosis.展开更多
The Sonic hedgehog (SHH) signaling pathway plays a pivotal role in neurogenesis and brain damage repair. Our previous work demonstrated that the SHH signaling pathway was involved in the neuroprotection of cortical ne...The Sonic hedgehog (SHH) signaling pathway plays a pivotal role in neurogenesis and brain damage repair. Our previous work demonstrated that the SHH signaling pathway was involved in the neuroprotection of cortical neurons against oxidative stress. The present study was aimed to further examine the underlying mechanism. The cortical neurons were obtained from one-day old Sprague-Dawley neonate rats. Hydrogen peroxide (H2O2, 100 μmol/L) was used to treat neurons for 24h to induce oxidative stress. Exogenous SHH (3μg/mL) was employed to activate the SHH pathway, and cyclopamine (20 μmol/L), a specific SHH signal inhibitor, to block SHH pathway. LY294002 (20 μmol/L) were used to pretreat the neurons 30 min before H2O2 treatment and selectively inhibit the phosphatidylinositol 3-kinase (PI3K)/Akt pathway. The cell viability was measured by MTT and apoptosis rate by flow cytometry analysis. The expression of p38, p-p38, ERK, p-ERK, Akt, p-Akt, Bcl-2, and Bax in neurons was detected by immunoblotting. The results showed that as compared with H2O2 treatment, exogenous SHH could increase the expression of p-Akt by 20% and decrease the expression of p-ERK by 33%. SHH exerted no significant effect on p38 mitogen-activated protein kinase (p38 MAPK) pathway. Blockade of PI3K/Akt pathway by LY294002 decreased the cell viability by 17% and increased the cell apoptosis rate by 2-fold. LY294002 treatment could up-regulate the expression of the proapoptotic gene Bax by 12% and down-regulate the expression of the antiapoptotic gene Bcl-2 by 54%. In conclusion, SHH pathway may activate PI3K/Akt pathway and inhibit the activation of the ERK pathway in neurons under oxidative stress. The PI3K/Akt pathway plays a key role in the neuroprotection of SHH. SHH/PI3K/Bcl-2 pathway may be implicated in the protection of neurons against H2O2-induced apoptosis.展开更多
HECT, UBA and WWE domain-containing 1(Huwe1), an E3 ubiquitin ligase involved in the ubiquitin-proteasome system, is widely expressed in brain tissue. Huwe1 is involved in the turnover of numerous substrates, includin...HECT, UBA and WWE domain-containing 1(Huwe1), an E3 ubiquitin ligase involved in the ubiquitin-proteasome system, is widely expressed in brain tissue. Huwe1 is involved in the turnover of numerous substrates, including p53, Mcl-1, Cdc6 and N-myc, thereby playing a critical role in apoptosis and neurogenesis. However, the role of Huwe1 in brain ischemia and reperfusion injury remains unclear. Therefore, in this study, we investigated the role of Huwe1 in an in vitro model of ischemia and reperfusion injury. At 3 days in vitro, primary cortical neurons were transduced with a control or shRNA-Huwe1 lentiviral vector to silence expression of Huwe1. At 7 days in vitro, the cells were exposed to oxygen-glucose deprivation for 3 hours and reperfusion for 24 hours. To examine the role of the c-Jun N-terminal kinase(JNK)/p38 pathway, cortical neurons were pretreated with a JNK inhibitor(SP600125) or a p38 MAPK inhibitor(SB203508) for 30 minutes at 7 days in vitro, followed by ischemia and reperfusion. Neuronal apoptosis was assessed by TUNEL assay. Protein expression levels of JNK and p38 MAPK and of apoptosis-related proteins(p53, Gadd45 a, cleaved caspase-3, Bax and Bcl-2) were measured by western blot assay. Immunofluorescence labeling for cleaved caspase-3 was performed. We observed a significant increase in neuronal apoptosis and Huwe1 expression after ischemia and reperfusion. Treatment with the shRNA-Huwe1 lentiviral vector markedly decreased Huwe1 levels, and significantly decreased the number of TUNEL-positive cells after ischemia and reperfusion. The silencing vector also downregulated the pro-apoptotic proteins Bax and cleaved caspase-3, and upregulated the anti-apoptotic proteins Gadd45 a and Bcl-2. Silencing Huwe1 also significantly reduced p-JNK levels and increased p-p38 levels. Our findings show that downregulating Huwe1 affects the JNK and p38 MAPK signaling pathways as well as the expression of apoptosis-related genes to provide neuroprotection during ischemia and reperfusion. All animal experiments and procedures were approved by the Animal Ethics Committee of Sichuan University, China in January 2018(approval No. 2018013).展开更多
Facial synkinesis,a sequela of peripheral facial nerve palsy,is characterized by simultaneous involuntary facial movement during a voluntary desired one.Maladaptive cortical plasticity might be involved in the dysfunc...Facial synkinesis,a sequela of peripheral facial nerve palsy,is characterized by simultaneous involuntary facial movement during a voluntary desired one.Maladaptive cortical plasticity might be involved in the dysfunction of facial muscles.This cohort study investigated the cortical functional alterations in patients with unilateral facial synkinesis,using the task functional magnetic resonance imaging.Facial motor tasks,including blinking and smiling,were performed by 16 patients（aged 30.6 ± 4.5 years,14 females/2 males） and 24 age-and sex-matched healthy controls（aged 29.1 ± 4.2 years,19 females/5 males）.Results demonstrated that activation in the cortico-facial motor representation area was lower during tasks in patients with facial synkinesis compared with healthy controls.Facial movements on either side performed by patients caused more intensive activation of the supplementary motor area on the contralateral side of the affected face,than those on the unaffected side.Our results revealed that there was cortical reorganization in the primary sensorimotor area and the supplementary motor area.This study was registered in Chinese Clinical Trial Registry（registration number： Chi CTR1800014630）.展开更多
Ectopic adrenal cortical neoplasms are extremely rare. Ectopic adrenocortical tissue can be found in locations such as the celiac axis,the broad ligament,the adnexa of the testes,and the spermatic cord;however,they ra...Ectopic adrenal cortical neoplasms are extremely rare. Ectopic adrenocortical tissue can be found in locations such as the celiac axis,the broad ligament,the adnexa of the testes,and the spermatic cord;however,they rarely involve the stomach.We report an unusual case of a patient with an ectopic adrenal cortical adenoma in the gastric wall.The patient was a 72-year old female admitted to our hospital with upper abdominal discomfort.Physical examination revealed tenderness below the xiphoid process.Both computed tomography and fibergastroscopy revealed a mass on the lesser curvature side of the gastric antrum;it was initially diagnosed as a gastric stromal tumor.After adequate preparation,the patient underwent surgery.During the procedure,we found a 30 mm×30 mm mass with medium density in the lesser curvature near the gastric antrum within the serosa.Following immunohistochemistry examination, we corrected the diagnosis to an ectopic adrenal cortical adenoma;the tumor was nonfunctional.展开更多
BACKGROUND： Ischemic stroke is often followed by the abnormalities of neurons and corticospinal tract, which can lead to corresponding clinical symptoms and signs. Recently, with the continuous perfection of high-fie...BACKGROUND： Ischemic stroke is often followed by the abnormalities of neurons and corticospinal tract, which can lead to corresponding clinical symptoms and signs. Recently, with the continuous perfection of high-field MRI instrument, it becomes possible to assess and investigate the cortical function and structural reconstruction following stroke by using MRI and diffusion tensor imaging （DTI）. OBJECTIVE： To observe the cortical motor function and changes of corticospinal tracts by using MRI and DTI in the patients with ischemic stroke at acute period, compare with the normal subjects, and assess the damage of corticospinal tract and muscle strength.DESIGN ： A case-control observation.SETTING： Department of Medical Imaging, Fuzhou General Hospital of Nanjing Military Area Command of Chinese PLA. PARTICIPANTS ： Nine inpatients （5 males and 4 females） with injury of motor function induced by acute ischemic stroke were selected from Fuzhou General Hospital of Nanjing Military Area Command of Chinese PLA between August and December in 2005, they aged 16-87 years with an average of 51 years old, and those with obvious conscious disturbances and severe cognitive disorders were excluded. At the same time, nine healthy right-handed physical examinees matched by age and gender with the patients were also selected, and they all had no nervous disease, epilepsy, mental diseases, cerebrovascular abnormalities and injury history, etc. All the subjects were informed with the detected items and agreed to participate in. METHODS： All the 9 patients with ischemic stroke at acute period and 9 healthy subjects were examined with MRI and DTI.① A block-based design was used in the MRI, the passive finger-to-finger exercise was used as the stimulative task, and the static condition was taken as the baseline task. The GE 1.5T MRI system was used, all the data were processed after off-line, and analyzed with the SPM2 software, the association between the activated area and local anatomy of brain was observed. ② The DTI image was processed with the dTV.Ⅱ.R1 software part of the anisotropic image and color anisotropic image were shown, and the three-dimensional white matter image of bilateral corticospinal tracts of the patients were reconstructed. ③ The muscle strength of the affected hand of the stroke patients was judged with the Brunnstorm standard. MAIN OUTCOME MEASURES： The manifestations of MRI, DTI and corticospinal tracts of the 9 stroke patients were mainly observed. RESULTS： All the 9 stroke patients and 9 healthy subjects were involved in the analysis of results. ① Results of MRI examination： The handed exercise of the healthy subjects mainly activated contralateral sensorimotor cortex, posterior parietal cortex and bilateral supplementary motor areas. For the exercise of ipsilateral hand of 7 stroke patients, contralateral sensorimotor cortex was weakly activated, but ipsilateral posterial parietal cortex was obviously activated, and the activation of cerebrum was observed in 3 of them. For the other two patients, bilateral sensorimotor cortexes were activated during the exercise of ipsilateral hand, and the ipsilateral activated area was greater than the controlateral one. The exercise of contralateral hand activated contralateral sensorimotor cortex, posterior parietal cortex and contralateral supplementary motor area, and no obvious ipsilateral activated area was observed.② Results of DTI examination： The anisotropic values of the infarcted area were obviously lower than those of the contralateral part （t=4.570, P 〈 0.01）. the anisotropic value of the infarcted area were obviously was obviously correlated with bilateral muscle strength （t=0.888, P 〈 0.05）. ③ Results of the examination for corticospinal tracts： The reconstruction of bilateral corticospinal tracts, contralateral anatomic form were generally identical with those of normal subjects, the consistency of each continuous form from anterior central gyrus downward to internal capsule to bridge of varolius and bulbus medullae. Because of the involvement of infarcted area to different extent, ipsilateral corticospinal tract was manifested by the interruption of succession and loss of consistency of anatomic structural form. The severity for the injury of corticospinal tract was markedly correlated with the muscle strength of the ipsilateral hand （r=0.888, P 〈 0.05）. CONCLUSION ： ① The MRI manifestations of stroke patients during the exercise of affected hand are different from those of normal subjects, suggesting that there is compensation and reconstruction of brain function.② DTI examination is good for the judgement of the correlation between the damaged severity of infarction and muscle strength.③The damaged severity of corticospinal tracts is correlated with muscle strength, and it can be used to judge the prognosis of rehabilitative treatment.展开更多
In the treatment of brachial plexus injury, nerves that are functionally less important are transferred onto the distal ends of damaged crucial nerves to help recover neuromuscular function in the target region. For e...In the treatment of brachial plexus injury, nerves that are functionally less important are transferred onto the distal ends of damaged crucial nerves to help recover neuromuscular function in the target region. For example, intercostal nerves are transferred onto axillary nerves, and accessory nerves are transferred onto suprascapular nerves, the phrenic nerve is transferred onto the musculocutaneous nerves, and the contralateral C7 nerve is transferred onto the median or radial nerves. Nerve transfer has become a major method for reconstructing the brachial plexus after avulsion injury. Many experiments have shown that nerve transfers for treatment of brachial plexus injury can help reconstruct cerebral cortical function and increase cortical plasticity. In this review article, we summarize the recent progress in the use of diverse nerve transfer methods for the repair of brachial plexus injury, and we discuss the impact of nerve transfer on cerebral cortical plasticity after brachial plexus injury.展开更多
基金supported by NIH/NIMH grant R01MH111619(to SQ),R21AG078700(to SQ)Institute of Mental Health Research(IMHR,Level 1 funding,to SQ and DF)institution startup fund from The University of Arizona(to SQ)。
文摘Loss of synapse and functional connectivity in brain circuits is associated with aging and neurodegeneration,however,few molecular mechanisms are known to intrinsically promote synaptogenesis or enhance synapse function.We have previously shown that MET receptor tyrosine kinase in the developing cortical circuits promotes dendritic growth and dendritic spine morphogenesis.To investigate whether enhancing MET in adult cortex has synapse regenerating potential,we created a knockin mouse line,in which the human MET gene expression and signaling can be turned on in adult(10–12 months)cortical neurons through doxycycline-containing chow.We found that similar to the developing brain,turning on MET signaling in the adult cortex activates small GTPases and increases spine density in prefrontal projection neurons.These findings are further corroborated by increased synaptic activity and transient generation of immature silent synapses.Prolonged MET signaling resulted in an increasedα-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid/N-methyl-Daspartate(AMPA/NMDA)receptor current ratio,indicative of enhanced synaptic function and connectivity.Our data reveal that enhancing MET signaling could be an interventional approach to promote synaptogenesis and preserve functional connectivity in the adult brain.These findings may have implications for regenerative therapy in aging and neurodegeneration conditions.
基金supported by the Natural Science Foundation of Guangdong Province,Nos.2019A1515010649(to WC),2022A1515012044(to JS)the China Postdoctoral Science Foundation,No.2018M633091(to JS).
文摘Transforming growth factor-beta 1(TGF-β1)has been extensively studied for its pleiotropic effects on central nervous system diseases.The neuroprotective or neurotoxic effects of TGF-β1 in specific brain areas may depend on the pathological process and cell types involved.Voltage-gated sodium channels(VGSCs)are essential ion channels for the generation of action potentials in neurons,and are involved in various neuroexcitation-related diseases.However,the effects of TGF-β1 on the functional properties of VGSCs and firing properties in cortical neurons remain unclear.In this study,we investigated the effects of TGF-β1 on VGSC function and firing properties in primary cortical neurons from mice.We found that TGF-β1 increased VGSC current density in a dose-and time-dependent manner,which was attributable to the upregulation of Nav1.3 expression.Increased VGSC current density and Nav1.3 expression were significantly abolished by preincubation with inhibitors of mitogen-activated protein kinase kinase(PD98059),p38 mitogen-activated protein kinase(SB203580),and Jun NH2-terminal kinase 1/2 inhibitor(SP600125).Interestingly,TGF-β1 significantly increased the firing threshold of action potentials but did not change their firing rate in cortical neurons.These findings suggest that TGF-β1 can increase Nav1.3 expression through activation of the ERK1/2-JNK-MAPK pathway,which leads to a decrease in the firing threshold of action potentials in cortical neurons under pathological conditions.Thus,this contributes to the occurrence and progression of neuroexcitatory-related diseases of the central nervous system.
文摘BACKGROUND The induced-membrane technique was initially described by Masquelet as an effective treatment for large bone defects,especially those caused by infection.Here,we report a case of chronic osteomyelitis of the radius associated with a 9 cm bone defect,which was filled with a large allogeneic cortical bone graft from a bone bank.Complete bony union was achieved after 14 months of follow-up.Previous studies have used autogenous bone as the primary bone source for the Masquelet technique;in our case,the exclusive use of allografts is as successful as the use of autologous bone grafts.With the advent of bone banks,it is possible to obtain an unlimited amount of allograft,and the Masquelet technique may be further improved based on this new way of bone grafting.CASE SUMMARY In this study,we reported a case of repair of a long bone defect in a 40-year-old male patient,which was characterized by the utilization of allograft cortical bone combined with the Masquelet technique for the treatment of the patient's long bone defect in the forearm.The patient's results of functional recovery of the forearm were surprising,which further deepens the scope of application of Masquelet technique and helps to strengthen the efficacy of Masquelet technique in the treatment of long bones indeed.CONCLUSION Allograft cortical bone combined with the Masquelet technique provides a new method of treatment to large bone defect.
文摘Objective: To study the relationship between cortical auditory evoked potential (CAEP) thresholds and behavioral thresholds in pediatric populations with sensorineural hearing loss (SNHL). Methods: Fifteen children (mean age 6.8 years) with bilateral SNHL underwent behavioral pure-tone audiometry and CAEP testing at 0.5, 1, 2, and 4 kHz. CAEP thresholds were determined using tone bursts, and correlations between CAEP and pure-tone thresholds were analyzed using Pearson correlation and t-tests. Results: A strong positive correlation was observed between P1 thresholds and behavioral thresholds across all test frequencies: 0.5 kHz (r = 0.765, p Conclusion: The strong correlation between P1 and behavioral thresholds demonstrates the reliability of CAEP testing for estimating auditory thresholds in children. These findings support the use of CAEP testing as a reliable objective tool for threshold estimation, particularly in cases where behavioral responses cannot be reliably obtained. When adjusted with frequency-specific correction values, CAEP testing provides a reliable method for assessing hearing thresholds in pediatric populations.
基金supported by the National Key R&D Program of China,No.2020YFC2004202(to DX).
文摘After stroke,even high-functioning individuals may experience compromised bimanual coordination and fine motor dexterity,leading to reduced functional independence.Bilateral arm training has been proposed as a promising intervention to address these deficits.However,the neural basis of the impairment of functional fine motor skills and their relationship to bimanual coordination performance in stroke patients remains unclear,limiting the development of more targeted interventions.To address this gap,our study employed functional near-infrared spectroscopy to investigate cortical responses in patients after stroke as they perform functional tasks that engage fine motor control and coordination.Twenty-four high-functioning patients with ischemic stroke(7 women,17 men;mean age 64.75±10.84 years)participated in this cross-sectional observational study and completed four subtasks from the Purdue Pegboard Test,which measures unimanual and bimanual finger and hand dexterity.We found significant bilateral activation of the sensorimotor cortices during all Purdue Pegboard Test subtasks,with bimanual tasks inducing higher cortical activation than the assembly subtask.Importantly,patients with better bimanual coordination exhibited lower cortical activation during the other three Purdue Pegboard Test subtasks.Notably,the observed neural response patterns varied depending on the specific subtask.In the unaffected hand task,the differences were primarily observed in the ipsilesional hemisphere.In contrast,the bilateral sensorimotor cortices and the contralesional hemisphere played a more prominent role in the bimanual task and assembly task,respectively.While significant correlations were found between cortical activation and unimanual tasks,no significant correlations were observed with bimanual tasks.This study provides insights into the neural basis of bimanual coordination and fine motor skills in high-functioning patients after stroke,highlighting task-dependent neural responses.The findings also suggest that patients who exhibit better bimanual performance demonstrate more efficient cortical activation.Therefore,incorporating bilateral arm training in post-stroke rehabilitation is important for better outcomes.The combination of functional near-infrared spectroscopy with functional motor paradigms is valuable for assessing skills and developing targeted interventions in stroke rehabilitation.
基金support from the National Natural Science Foundation of China(Nos.52073230,62204204,and 62288102)the Shaanxi Provincial Science Fund for Distinguished Young Scholars(No.2023-JC-JQ-32)+2 种基金the Science and Technology Innovation 2030-Major Project(No.2022ZD0208601)the Shanghai Sailing Program(No.21YF1451000)the China National Postdoctoral Program for Innovative Talents(No.BX20230494).
文摘Cortical electrodes are a powerful tool for the stimulation and/or recording of electrical activity in the nervous system.However,the inevitable wound caused by surgical implantation of electrodes presents bacterial infection and inflammatory reaction risks associated with foreign body exposure.Moreover,inflammation of the wound area can dramatically worsen in response to bacterial infection.These consequences can not only lead to the failure of cortical electrode implantation but also threaten the lives of patients.Herein,we prepared a hydrogel made of bacterial cellulose(BC),a flexible substrate for cortical electrodes,and further loaded antibiotic tetracycline(TC)and the anti-inflammatory drug dexamethasone(DEX)onto it.The encapsulated drugs can be released from the BC hydrogel and effectively inhibit the growth of Gram-negative and Gram-positive bacteria.Next,therapeutic cortical electrodes were developed by integrating the drug-loaded BC hydrogel and nine-channel serpentine arrays;these were used to record electrocorticography(ECoG)signals in a rat model.Due to the controlled release of TC and DEX from the BC hydrogel substrate,therapeutic cortical electrodes can alleviate or prevent symptoms associated with the bacterial infection and inflammation of brain tissue.This approach facilitates the development of drug delivery electrodes for resolving complications caused by implantable electrodes.
基金supported by the National Natural Science Foundation of China(Major Project),No.82030110(to CYM)the National Natural Science Foundation(Youth Program),No.82003754(to SNW)+1 种基金Medical Innovation Major Project,No.16CXZ009(to CYM)Shanghai Science and Technology Commission Projects,Nos.20YF1458400(to SNW)and 21140901000(to CYM)。
文摘As three-dimensional“organ-like”aggregates,human cortical organoids have emerged as powerful models for studying human brain evolution and brain disorders with unique advantages of humanspecificity,fidelity and manipulation.Human cortical organoids derived from human pluripotent stem cells can elaborately replicate many of the key properties of human cortical development at the molecular,cellular,structural,and functional levels,including the anatomy,functional neural network,and interaction among different brain regions,thus facilitating the discovery of brain development and evolution.In addition to studying the neuro-electrophysiological features of brain cortex development,human cortical organoids have been widely used to mimic the pathophysiological features of cortical-related disease,especially in mimicking malformations of cortical development,thus revealing pathological mechanism and identifying effective drugs.In this review,we provide an overview of the generation of human cortical organoids and the properties of recapitulated cortical development and further outline their applications in modeling malformations of cortical development including pathological phenotype,underlying mechanisms and rescue strategies.
基金supported by the National Natural Science Foundation of China(Grant Nos.12372363,12272254,and 12072219)the special fund for Science and Technology Innovation Teams of Shanxi Province(Grant No.202204051002006)+1 种基金the Natural Science Foundation of Shanxi Province(Grant No.202203021211170)the project of Key Laboratory of Impact and Safety Engineering(Ningbo University),Ministry of Education(Grant No.CJ202202)。
文摘Bone is a multi-phase,non-homogeneous material that exhibits strain rate sensitivity,and it may fail under compression,tension,torsion,or a combination of these loading.The mechanical properties of cortical bone with strain rate effect under compression and tension have been obtained through the application of the split Hopkinson pressure/tension bar technique,but no such studies have been reported for determining the strain rate behavior properties of bony materials under torsion.In this study,the shear stress-strain curves with the rate-dependent cortical bone subjected to dynamic torsional loading were first obtained using a torsional split Hopkinson bar system.Based on the experiments,an improved mathematical model consisting of elastic,viscoelastic,and viscoplastic components was used to identify the material parameters of the cortical bone.Detailed material properties are derived through constitutive relations.The results may assist researchers in developing more accurate models of cortical bone behavior under different load conditions.
文摘Background: We present a compelling case fitting the phenomenon of cortical spreading depression detected by intraoperative neurophysiological monitoring (IONM) following an intraoperative seizure during a craniotomy for revascularization. Cortical spreading depression (CSD, also called cortical spreading depolarization) is a pathophysiological phenomenon whereby a wave of depolarization is thought to propagate across the cerebral cortex, creating a brief period of relative neuronal inactivity. The relationship between CSD and seizures is unclear, although some literature has made a correlation between seizures and a cortical environment conducive to CSD. Methods: Intraoperative somatosensory evoked potentials (SSEPs) and electroencephalography (EEG) were monitored continuously during the craniotomy procedure utilizing standard montages. Electrophysiological data from pre-ictal, ictal, and post-ictal periods were recorded. Results: During the procedure, intraoperative EEG captured a generalized seizure followed by a stepwise decrease in somatosensory evoked potential cortical amplitudes, compelling for the phenomenon of CSD. The subsequent partial recovery of neuronal function was also captured electrophysiologically. Discussion: While CSD is considered controversial in some aspects, intraoperative neurophysiological monitoring allowed for the unique analysis of a case demonstrating a CSD-like phenomenon. To our knowledge, this is the first published example of this phenomenon in which intraoperative neurophysiological monitoring captured a seizure, along with a stepwise subsequent reduction in SSEP cortical amplitudes not explained by other variables.
文摘Aim: To study the effects of rhynchophylline (Rhy) on the L type calcium channels in freshly dissociated cortical neurons of Wistar rats during acute hypoxia. Methods: Cell attached configuration of patch clamp technique. L type calcium channel was activated by stepping from 40 mV to 0 mV. Results: The results showed that the L type calcium channels of cortical neurons were activated by acute hypoxia. The mean open time of the channel was increased, the mean close time decreased and the open state probability raised during acute hypoxia. Rhy (15 and 30μmol·L -1 ) in concentration dependent manner blocked activity of the channels. The drug shortened the mean open time of the channels from 8 87 ms to 3 03 ms and 2 23 ms ( P 【0 001), prolonged the mean close time from 9 23 ms to 38 84 ms and 54 43 ms ( P 【0 001), and decreased the open state probability from 0 142 to 0 031 and 0 025 ( P 【0 001) under the hypoxia condition, respectively. The effects of Rhy were similar to but weaker than those of verapamil (15 μmol·L -1 ). Conclusion: The study confirmed that Rhy has the blockade effects on L type calcium channels in cortical neurons of rats during hypoxia, by which it protects the brain from hypoxic injury.
基金National Natural Science Foundation of China (31171082)Natural Science Foundation of Anhui Province (070413138)Key Research Foundation of Anhui Province Education Department (KJ2009A167)
文摘Psychophysical studies suggest that lateral extrastriate visual cortical areas in cats may mediate the sparing of vision largely by network reorganization following lesions of early visual cortical areas. To date, however, there is little direct physiological evidence to support this hypothesis. Using in vivo single-anit recording techniques, we examined the response of neurons in areas 19, 21, and 20 to different types of visual stimulation in cats with or without acute bilateral lesions in areas 17 and 18. Our results showed that, relative to the controls, acute lesions inactivated the response of 99.3% of neurons to moving gratings and 93% of neurons to flickering square stimuli＇in areas 19, 21, and 20. These results indicated that acute lesions of primary visual areas in adult eats may impair most visual abilities. Sparing of vision in cats with neonatal lesions in early visual cortical areas may result largely from a postoperative reorganization of visual pathways from subcortical nucleus to extrastriate visual cortical areas.
基金supported by the Key Laboratory of Trauma and Neural Regeneration (Peking University),Ministry of Education of China,No. BMU2020XY005-03National Natural Science Foundation of China,No. 31771322+2 种基金Beijing Science&Technology New Star Cross Project of China,No. 201819Major R&D Program of National Ministry of Science and Technology of China,No. 2018YFB1105504a grant from National Center for Trauma Medicine,Beijing,China,No. BMU2020XY005-01 (all to PXZ)。
文摘With the development of neuroscience, substantial advances have been achieved in peripheral nerve regeneration over the past decades. However, peripheral nerve injury remains a critical public health problem because of the subsequent impairment or absence of sensorimotor function. Uncomfortable complications of peripheral nerve injury, such as chronic pain, can also cause problems for families and society. A number of studies have demonstrated that the proper functioning of the nervous system depends not only on a complete connection from the central nervous system to the surrounding targets at an anatomical level, but also on the continuous bilateral communication between the two. After peripheral nerve injury, the interruption of afferent and efferent signals can cause complex pathophysiological changes, including neurochemical alterations, modifications in the adaptability of excitatory and inhibitory neurons, and the reorganization of somatosensory and motor regions. This review discusses the close relationship between the cerebral cortex and peripheral nerves. We also focus on common therapies for peripheral nerve injury and summarize their potential mechanisms in relation to cortical plasticity. It has been suggested that cortical plasticity may be important for improving functional recovery after peripheral nerve damage. Further understanding of the potential common mechanisms between cortical reorganization and nerve injury will help to elucidate the pathophysiological processes of nerve injury, and may allow for the reduction of adverse consequences during peripheral nerve injury recovery. We also review the role that regulating reorganization mechanisms plays in functional recovery, and conclude with a suggestion to target cortical plasticity along with therapeutic interventions to promote peripheral nerve injury recovery.
基金supported by the National Nature Science Foundation of China (no.30972229 and 31101866)a project Funded by Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD)
文摘Objective To investigate the cytotoxic mechanism of cadmium（Cd） on cerebral cortical neurons.Methods The primary cultures of rat cerebral cortical neurons were treated with different concentrations of cadmium acetate（0,5,10,and 20 μmol/L）,and then the cell viability,apoptosis,ultrastructure,intracellular [Ca2＋]i and reactive oxygen species（ROS） levels,mitochondrial membrane potential（ΔΨ）,activities of catalase（CAT） and superoxide dismutase（SOD） were measured.Results A progressive loss in cell viability and an increased number of apoptotic cells were observed.In addition,Cd-induced apoptotic morphological changes in cerebral cortical neurons were also demonstrated by Hoechst 33258 staining.Meanwhile,ultrastructural changes were distortion of mitochondrial cristae and an unusual arrangement.Simultaneously,elevation of intracellular [Ca2＋]i and ROS levels,depletion of ΔΨ were revealed in a dose-dependent manner during the exposure.Moreover,CAT and SOD activities in the living cells increased significantly.Conclusion Exposure of cortical neurons to different doses of Cd led to cellular death,mediated by an apoptotic mechanism,and the apoptotic death induced by oxidative stress may be a potential reason.And the disorder of intracellular homeostasis caused by oxidative stress and mitochondrial dysfunction may be a trigger for apoptosis in cortical neurons.
文摘The coexistence of myelolipoma within adrenal cortical adenoma is extremely rare,for both tumors present usually as separate entities.There are only 16 such cases reported worldwide.To the best of our knowledge,the case we reported here is the first one of myxoid adrenal cortical adenoma associated with myelolipoma reported.A 32-year-old Chinese woman with 4-year history of hypertension was presented in our study.Computed tomography(CT)of the abdomen showed a large heterogene- ously-enhancing mass(4.5 cm in diameter)in the left suprarenal region.Clinical history and laboratory results suggest a metabolic disorder as Conn's syndrome.The patient underwent a left adrenalectomy,and a histopathological study confirmed the mass to be a myxoid adrenal cortical adenoma containing myelolipoma.The patient was postoperatively well and discharged uneventfully.In the present case report,we also discuss the etiology of simultaneous myelolipoma and adrenal adenoma associated with Conn's syndrome,and the methods of the diagnosis and differential diagnosis.
基金supported by a grant from the National Natural Science Foundation of China(No.81070938)
文摘The Sonic hedgehog (SHH) signaling pathway plays a pivotal role in neurogenesis and brain damage repair. Our previous work demonstrated that the SHH signaling pathway was involved in the neuroprotection of cortical neurons against oxidative stress. The present study was aimed to further examine the underlying mechanism. The cortical neurons were obtained from one-day old Sprague-Dawley neonate rats. Hydrogen peroxide (H2O2, 100 μmol/L) was used to treat neurons for 24h to induce oxidative stress. Exogenous SHH (3μg/mL) was employed to activate the SHH pathway, and cyclopamine (20 μmol/L), a specific SHH signal inhibitor, to block SHH pathway. LY294002 (20 μmol/L) were used to pretreat the neurons 30 min before H2O2 treatment and selectively inhibit the phosphatidylinositol 3-kinase (PI3K)/Akt pathway. The cell viability was measured by MTT and apoptosis rate by flow cytometry analysis. The expression of p38, p-p38, ERK, p-ERK, Akt, p-Akt, Bcl-2, and Bax in neurons was detected by immunoblotting. The results showed that as compared with H2O2 treatment, exogenous SHH could increase the expression of p-Akt by 20% and decrease the expression of p-ERK by 33%. SHH exerted no significant effect on p38 mitogen-activated protein kinase (p38 MAPK) pathway. Blockade of PI3K/Akt pathway by LY294002 decreased the cell viability by 17% and increased the cell apoptosis rate by 2-fold. LY294002 treatment could up-regulate the expression of the proapoptotic gene Bax by 12% and down-regulate the expression of the antiapoptotic gene Bcl-2 by 54%. In conclusion, SHH pathway may activate PI3K/Akt pathway and inhibit the activation of the ERK pathway in neurons under oxidative stress. The PI3K/Akt pathway plays a key role in the neuroprotection of SHH. SHH/PI3K/Bcl-2 pathway may be implicated in the protection of neurons against H2O2-induced apoptosis.
基金supported by the National Natural Science Foundation of China,No.81771642(to WMX)the New Bud Research Foundation of West China Second University Hospital of China(to GQH)
文摘HECT, UBA and WWE domain-containing 1(Huwe1), an E3 ubiquitin ligase involved in the ubiquitin-proteasome system, is widely expressed in brain tissue. Huwe1 is involved in the turnover of numerous substrates, including p53, Mcl-1, Cdc6 and N-myc, thereby playing a critical role in apoptosis and neurogenesis. However, the role of Huwe1 in brain ischemia and reperfusion injury remains unclear. Therefore, in this study, we investigated the role of Huwe1 in an in vitro model of ischemia and reperfusion injury. At 3 days in vitro, primary cortical neurons were transduced with a control or shRNA-Huwe1 lentiviral vector to silence expression of Huwe1. At 7 days in vitro, the cells were exposed to oxygen-glucose deprivation for 3 hours and reperfusion for 24 hours. To examine the role of the c-Jun N-terminal kinase(JNK)/p38 pathway, cortical neurons were pretreated with a JNK inhibitor(SP600125) or a p38 MAPK inhibitor(SB203508) for 30 minutes at 7 days in vitro, followed by ischemia and reperfusion. Neuronal apoptosis was assessed by TUNEL assay. Protein expression levels of JNK and p38 MAPK and of apoptosis-related proteins(p53, Gadd45 a, cleaved caspase-3, Bax and Bcl-2) were measured by western blot assay. Immunofluorescence labeling for cleaved caspase-3 was performed. We observed a significant increase in neuronal apoptosis and Huwe1 expression after ischemia and reperfusion. Treatment with the shRNA-Huwe1 lentiviral vector markedly decreased Huwe1 levels, and significantly decreased the number of TUNEL-positive cells after ischemia and reperfusion. The silencing vector also downregulated the pro-apoptotic proteins Bax and cleaved caspase-3, and upregulated the anti-apoptotic proteins Gadd45 a and Bcl-2. Silencing Huwe1 also significantly reduced p-JNK levels and increased p-p38 levels. Our findings show that downregulating Huwe1 affects the JNK and p38 MAPK signaling pathways as well as the expression of apoptosis-related genes to provide neuroprotection during ischemia and reperfusion. All animal experiments and procedures were approved by the Animal Ethics Committee of Sichuan University, China in January 2018(approval No. 2018013).
基金supported by the Youth Researcher Foundation of Shanghai Municipal Commission of Health and Family Planning,No.20144Y0095
文摘Facial synkinesis,a sequela of peripheral facial nerve palsy,is characterized by simultaneous involuntary facial movement during a voluntary desired one.Maladaptive cortical plasticity might be involved in the dysfunction of facial muscles.This cohort study investigated the cortical functional alterations in patients with unilateral facial synkinesis,using the task functional magnetic resonance imaging.Facial motor tasks,including blinking and smiling,were performed by 16 patients（aged 30.6 ± 4.5 years,14 females/2 males） and 24 age-and sex-matched healthy controls（aged 29.1 ± 4.2 years,19 females/5 males）.Results demonstrated that activation in the cortico-facial motor representation area was lower during tasks in patients with facial synkinesis compared with healthy controls.Facial movements on either side performed by patients caused more intensive activation of the supplementary motor area on the contralateral side of the affected face,than those on the unaffected side.Our results revealed that there was cortical reorganization in the primary sensorimotor area and the supplementary motor area.This study was registered in Chinese Clinical Trial Registry（registration number： Chi CTR1800014630）.
文摘Ectopic adrenal cortical neoplasms are extremely rare. Ectopic adrenocortical tissue can be found in locations such as the celiac axis,the broad ligament,the adnexa of the testes,and the spermatic cord;however,they rarely involve the stomach.We report an unusual case of a patient with an ectopic adrenal cortical adenoma in the gastric wall.The patient was a 72-year old female admitted to our hospital with upper abdominal discomfort.Physical examination revealed tenderness below the xiphoid process.Both computed tomography and fibergastroscopy revealed a mass on the lesser curvature side of the gastric antrum;it was initially diagnosed as a gastric stromal tumor.After adequate preparation,the patient underwent surgery.During the procedure,we found a 30 mm×30 mm mass with medium density in the lesser curvature near the gastric antrum within the serosa.Following immunohistochemistry examination, we corrected the diagnosis to an ectopic adrenal cortical adenoma;the tumor was nonfunctional.
基金the Natural Science Foundation of Fujian Province, No. Z0516079
文摘BACKGROUND： Ischemic stroke is often followed by the abnormalities of neurons and corticospinal tract, which can lead to corresponding clinical symptoms and signs. Recently, with the continuous perfection of high-field MRI instrument, it becomes possible to assess and investigate the cortical function and structural reconstruction following stroke by using MRI and diffusion tensor imaging （DTI）. OBJECTIVE： To observe the cortical motor function and changes of corticospinal tracts by using MRI and DTI in the patients with ischemic stroke at acute period, compare with the normal subjects, and assess the damage of corticospinal tract and muscle strength.DESIGN ： A case-control observation.SETTING： Department of Medical Imaging, Fuzhou General Hospital of Nanjing Military Area Command of Chinese PLA. PARTICIPANTS ： Nine inpatients （5 males and 4 females） with injury of motor function induced by acute ischemic stroke were selected from Fuzhou General Hospital of Nanjing Military Area Command of Chinese PLA between August and December in 2005, they aged 16-87 years with an average of 51 years old, and those with obvious conscious disturbances and severe cognitive disorders were excluded. At the same time, nine healthy right-handed physical examinees matched by age and gender with the patients were also selected, and they all had no nervous disease, epilepsy, mental diseases, cerebrovascular abnormalities and injury history, etc. All the subjects were informed with the detected items and agreed to participate in. METHODS： All the 9 patients with ischemic stroke at acute period and 9 healthy subjects were examined with MRI and DTI.① A block-based design was used in the MRI, the passive finger-to-finger exercise was used as the stimulative task, and the static condition was taken as the baseline task. The GE 1.5T MRI system was used, all the data were processed after off-line, and analyzed with the SPM2 software, the association between the activated area and local anatomy of brain was observed. ② The DTI image was processed with the dTV.Ⅱ.R1 software part of the anisotropic image and color anisotropic image were shown, and the three-dimensional white matter image of bilateral corticospinal tracts of the patients were reconstructed. ③ The muscle strength of the affected hand of the stroke patients was judged with the Brunnstorm standard. MAIN OUTCOME MEASURES： The manifestations of MRI, DTI and corticospinal tracts of the 9 stroke patients were mainly observed. RESULTS： All the 9 stroke patients and 9 healthy subjects were involved in the analysis of results. ① Results of MRI examination： The handed exercise of the healthy subjects mainly activated contralateral sensorimotor cortex, posterior parietal cortex and bilateral supplementary motor areas. For the exercise of ipsilateral hand of 7 stroke patients, contralateral sensorimotor cortex was weakly activated, but ipsilateral posterial parietal cortex was obviously activated, and the activation of cerebrum was observed in 3 of them. For the other two patients, bilateral sensorimotor cortexes were activated during the exercise of ipsilateral hand, and the ipsilateral activated area was greater than the controlateral one. The exercise of contralateral hand activated contralateral sensorimotor cortex, posterior parietal cortex and contralateral supplementary motor area, and no obvious ipsilateral activated area was observed.② Results of DTI examination： The anisotropic values of the infarcted area were obviously lower than those of the contralateral part （t=4.570, P 〈 0.01）. the anisotropic value of the infarcted area were obviously was obviously correlated with bilateral muscle strength （t=0.888, P 〈 0.05）. ③ Results of the examination for corticospinal tracts： The reconstruction of bilateral corticospinal tracts, contralateral anatomic form were generally identical with those of normal subjects, the consistency of each continuous form from anterior central gyrus downward to internal capsule to bridge of varolius and bulbus medullae. Because of the involvement of infarcted area to different extent, ipsilateral corticospinal tract was manifested by the interruption of succession and loss of consistency of anatomic structural form. The severity for the injury of corticospinal tract was markedly correlated with the muscle strength of the ipsilateral hand （r=0.888, P 〈 0.05）. CONCLUSION ： ① The MRI manifestations of stroke patients during the exercise of affected hand are different from those of normal subjects, suggesting that there is compensation and reconstruction of brain function.② DTI examination is good for the judgement of the correlation between the damaged severity of infarction and muscle strength.③The damaged severity of corticospinal tracts is correlated with muscle strength, and it can be used to judge the prognosis of rehabilitative treatment.
基金supported by grants from the General Project funded by Shanghai Municipal Health Bureau in China,No.20124328the General Program funded by Shanghai Municipal Science and Technology Commission in China,No.13ZR434100+1 种基金the National Natural Science Foundation of China,No.81201468Shanghai Key Laboratory of Peripheral Nerve and Microsurgery,No.08D22270600
文摘In the treatment of brachial plexus injury, nerves that are functionally less important are transferred onto the distal ends of damaged crucial nerves to help recover neuromuscular function in the target region. For example, intercostal nerves are transferred onto axillary nerves, and accessory nerves are transferred onto suprascapular nerves, the phrenic nerve is transferred onto the musculocutaneous nerves, and the contralateral C7 nerve is transferred onto the median or radial nerves. Nerve transfer has become a major method for reconstructing the brachial plexus after avulsion injury. Many experiments have shown that nerve transfers for treatment of brachial plexus injury can help reconstruct cerebral cortical function and increase cortical plasticity. In this review article, we summarize the recent progress in the use of diverse nerve transfer methods for the repair of brachial plexus injury, and we discuss the impact of nerve transfer on cerebral cortical plasticity after brachial plexus injury.
