Cholesterol is an important component of plasma membranes and participates in many basic life functions,such as the maintenance of cell membrane stability,the synthesis of steroid hormones,and myelination.Cholesterol ...Cholesterol is an important component of plasma membranes and participates in many basic life functions,such as the maintenance of cell membrane stability,the synthesis of steroid hormones,and myelination.Cholesterol plays a key role in the establishment and maintenance of the central nervous system.The brain contains 20%of the whole body’s cholesterol,80%of which is located within myelin.A huge number of processes(e.g.,the sterol regulatory element-binding protein pathway and liver X receptor pathway)participate in the regulation of cholesterol metabolism in the brain via mechanisms that include cholesterol biosynthesis,intracellular transport,and efflux.Certain brain injuries or diseases involving crosstalk among the processes above can affect normal cholesterol metabolism to induce detrimental consequences.Therefore,we hypothesized that cholesterol-related molecules and pathways can serve as therapeutic targets for central nervous system diseases.Intracerebral hemorrhage is the most severe hemorrhagic stroke subtype,with high mortality and morbidity.Historical cholesterol levels are associated with the risk of intracerebral hemorrhage.Moreover,secondary pathological changes after intracerebral hemorrhage are associated with cholesterol metabolism dysregulation,such as neuroinflammation,demyelination,and multiple types of programmed cell death.Intracellular cholesterol accumulation in the brain has been found after intracerebral hemorrhage.In this paper,we review normal cholesterol metabolism in the central nervous system,the mechanisms known to participate in the disturbance of cholesterol metabolism after intracerebral hemorrhage,and the links between cholesterol metabolism and cell death.We also review several possible and constructive therapeutic targets identified based on cholesterol metabolism to provide cholesterol-based perspectives and a reference for those interested in the treatment of intracerebral hemorrhage.展开更多
In the article titled“Neuroprotection mediated by the Wnt/Frizzled signaling pathway in early brain injury induced by subarachnoid hemorrhage,”published on pages 1013-1024,Issue 6,Volume 14 of Neural Regeneration Re...In the article titled“Neuroprotection mediated by the Wnt/Frizzled signaling pathway in early brain injury induced by subarachnoid hemorrhage,”published on pages 1013-1024,Issue 6,Volume 14 of Neural Regeneration Research(Wang et al.,2019),there are some errors in selecting the appropriate images in Figures 4A,4B,and 5A by authors during assembling the images.展开更多
In this article,we comment on the paper by Kakinuma et al published recently.We focus specifically on the diagnosis of uterine pseudoaneurysm,but we also review other uterine vascular anomalies that may be the cause o...In this article,we comment on the paper by Kakinuma et al published recently.We focus specifically on the diagnosis of uterine pseudoaneurysm,but we also review other uterine vascular anomalies that may be the cause of life-threating hemorrhage and the different causes of uterine pseudoaneurysms.Uterine artery pseudoaneurysm is a complication of both surgical gynecological and nontraumatic procedures.Massive hemorrhage is the consequence of the rupture of the pseudoaneurysm.Uterine artery pseudoaneurysm can develop after obstetric or gynecological procedures,being the most frequent after cesarean or vaginal deliveries,curettage and even during pregnancy.However,there are several cases described unrelated to pregnancy,such as after conization,hysteroscopic surgery or laparoscopic myomectomy.Hemorrhage is the clinical manifestation and it can be life-threatening so suspicion of this vascular lesion is essential for early diagnosis and treatment.However,there are other uterine vascular anomalies that may be the cause of severe hemorrhage,which must be taken into account in the differential diagnosis.Computed tomography angiography and embolization is supposed to be the first therapeutic option in most of them.展开更多
Aneurysm rupture can result in subarachnoid hemorrhage,a condition with potentially severe consequences,such as disability and death.In the acute stage,early brain injury manifests as intracranial pressure elevation,g...Aneurysm rupture can result in subarachnoid hemorrhage,a condition with potentially severe consequences,such as disability and death.In the acute stage,early brain injury manifests as intracranial pressure elevation,global cerebral ischemia,acute hydrocephalus,and direct blood–brain contact due to aneurysm rupture.This may subsequently cause delayed cerebral infarction,often with cerebral vasospasm,significantly affecting patient outcomes.Chronic complications such as brain volume loss and chronic hydrocephalus can further impact outcomes.Investigating the mechanisms of subarachnoid hemorrhage-induced brain injury is paramount for identifying effective treatments.Stem cell therapy,with its multipotent differentiation capacity and anti-inflammatory effects,has emerged as a promising approach for treating previously deemed incurable conditions.This review focuses on the potential application of stem cells in subarachnoid hemorrhage pathology and explores their role in neurogenesis and as a therapeutic intervention in preclinical and clinical subarachnoid hemorrhage studies.展开更多
Subarachnoid hemorrhage leads to a series of pathological changes,including vascular spasm,cellular apoptosis,blood–brain barrier damage,cerebral edema,and white matter injury.Microglia,which are the key immune cells...Subarachnoid hemorrhage leads to a series of pathological changes,including vascular spasm,cellular apoptosis,blood–brain barrier damage,cerebral edema,and white matter injury.Microglia,which are the key immune cells in the central nervous system,maintain homeostasis in the neural environment,support neurons,mediate apoptosis,participate in immune regulation,and have neuroprotective effects.Increasing evidence has shown that microglia play a pivotal role in the pathogenesis of subarachnoid hemorrhage and affect the process of injury and the prognosis of subarachnoid hemorrhage.Moreover,microglia play certain neuroprotective roles in the recovery phase of subarachnoid hemorrhage.Several approaches aimed at modulating microglia function are believed to attenuate subarachnoid hemorrhage injury.This provides new targets and ideas for the treatment of subarachnoid hemorrhage.However,an in-depth and comprehensive summary of the role of microglia after subarachnoid hemorrhage is still lacking.This review describes the activation of microglia after subarachnoid hemorrhage and their roles in the pathological processes of vasospasm,neuroinflammation,neuronal apoptosis,blood–brain barrier disruption,cerebral edema,and cerebral white matter lesions.It also discusses the neuroprotective roles of microglia during recovery from subarachnoid hemorrhage and therapeutic advances aimed at modulating microglial function after subarachnoid hemorrhage.Currently,microglia in subarachnoid hemorrhage are targeted with TLR inhibitors,nuclear factor-κB and STAT3 pathway inhibitors,glycine/tyrosine kinases,NLRP3 signaling pathway inhibitors,Gasdermin D inhibitors,vincristine receptorαreceptor agonists,ferroptosis inhibitors,genetic modification techniques,stem cell therapies,and traditional Chinese medicine.However,most of these are still being evaluated at the laboratory stage.More clinical studies and data on subarachnoid hemorrhage are required to improve the treatment of subarachnoid hemorrhage.展开更多
Cerebral edema caused by blood-brain barrier injury after intracerebral hemorrhage is an important factor leading to poor prognosis.Human-induced pluripotent stem cell-derived neural stem cell exosomes(hiPSC-NSC-Exos)...Cerebral edema caused by blood-brain barrier injury after intracerebral hemorrhage is an important factor leading to poor prognosis.Human-induced pluripotent stem cell-derived neural stem cell exosomes(hiPSC-NSC-Exos)have shown potential for brain injury repair in central nervous system diseases.In this study,we explored the impact of hiPSC-NSC-Exos on blood-brain barrier preservation and the underlying mechanism.Our results indicated that intranasal delivery of hiPSC-NSC-Exos mitigated neurological deficits,enhanced blood-brain barrier integrity,and reduced leukocyte infiltration in a mouse model of intracerebral hemorrhage.Additionally,hiPSC-NSC-Exos decreased immune cell infiltration,activated astrocytes,and decreased the secretion of inflammatory cytokines like monocyte chemoattractant protein-1,macrophage inflammatory protein-1α,and tumor necrosis factor-αpost-intracerebral hemorrhage,thereby improving the inflammatory microenvironment.RNA sequencing indicated that hiPSC-NSC-Exo activated the PI3K/AKT signaling pathway in astrocytes and decreased monocyte chemoattractant protein-1 secretion,thereby improving blood-brain barrier integrity.Treatment with the PI3K/AKT inhibitor LY294002 or the monocyte chemoattractant protein-1 neutralizing agent C1142 abolished these effects.In summary,our findings suggest that hiPSC-NSC-Exos maintains blood-brain barrier integrity,in part by downregulating monocyte chemoattractant protein-1 secretion through activation of the PI3K/AKT signaling pathway in astrocytes.展开更多
Intracerebral hemorrhage(ICH)is a common severe emergency in neurosurgery,causing tremendous economic pressure on families and society and devastating effects on patients both physically and psychologically,especially...Intracerebral hemorrhage(ICH)is a common severe emergency in neurosurgery,causing tremendous economic pressure on families and society and devastating effects on patients both physically and psychologically,especially among patients with poor functional outcomes.ICH is often accompanied by decreased consciousness and limb dysfunction.This seriously affects patients’ability to live independently.Although rapid advances in neurosurgery have greatly improved patient survival,there remains insufficient evidence that surgical treatment significantly improves long-term outcomes.With in-depth pathophysiological studies after ICH,increasing evidence has shown that secondary injury after ICH is related to long-term prognosis and that the key to secondary injury is various immune-mediated neuroinflammatory reactions after ICH.In basic and clinical studies of various systemic inflammatory diseases,triggering receptor expressed on myeloid cells 1/2(TREM-1/2),and the TREM receptor family is closely related to the inflammatory response.Various inflammatory diseases can be upregulated and downregulated through receptor intervention.How the TREM receptor functions after ICH,the types of results from intervention,and whether the outcomes can improve secondary brain injury and the long-term prognosis of patients are unknown.An analysis of relevant research results from basic and clinical trials revealed that the inhibition of TREM-1 and the activation of TREM-2 can alleviate the neuroinflammatory immune response,significantly improve the long-term prognosis of neurological function in patients with cerebral hemorrhage,and thus improve the ability of patients to live independently.展开更多
Background: Bilateral adrenal hemorrhage (BAH) is a rare condition that may lead to life-threatening adrenal insufficiency or adrenal crisis if not addressed appropriately. Case Report: A 54-year-old male with a histo...Background: Bilateral adrenal hemorrhage (BAH) is a rare condition that may lead to life-threatening adrenal insufficiency or adrenal crisis if not addressed appropriately. Case Report: A 54-year-old male with a history of venous thromboembolism (VTE) on warfarin presented to the hospital with nausea, vomiting, and abdominal and flank pain shortly following colonoscopy preparation. Initial imaging of the abdomen and pelvis was notable for hyperdense thickening of the bilateral adrenal glands raising concerns for hemorrhages, and subsequent magnetic resonance imaging (MRI) confirmed BAH. During hospitalization, the patient was placed on prophylactic heparin, and shortly after decompensating, he became tachycardic, hypotensive, and febrile. This led to heparin reversal followed by administration of a single dose of Hydrocortisone 100 mg and Hydrocortisone 50 mg TID due to concern for adrenal insufficiency. The patient also necessitated sepsis work-up and fluid resuscitation. Repeat CT imaging showed no significant change in hemorrhage size bilaterally. Endocrinology, vascular surgery, hematology/oncology, and rheumatology were consulted for the management of adrenal insufficiency, anticoagulation in the presence of hemorrhage, thrombocytopenia, and hypercoagulable state. Towards the end of his hospital course, the patient had asymptomatic diffuse ST elevations, elevated troponin, and an ejection fraction of 10% - 15%, leading to cardiac catheterization and placement of an intra-aortic pump. During subsequent stay in the ICU, the patient developed hemodynamic shock and was transferred to a facility with a higher level of care and medical support therapies. After this transfer, the patient was stabilized from a cardiac standpoint but developed acute respiratory failure suspected to be secondary to diffuse alveolar hemorrhage and immune thrombocytopenic purpura, necessitating platelet transfusion. He was on continued monitoring from rheumatology given his myocarditis believed to be secondary to his antiphospholipid antibodies, and was treated with IVIG, rituximab, and hydroxychloroquine. A repeat echocardiogram revealed an improved ejection fraction of 52% and the patient was then discharged on an enoxaparin bridge to warfarin and a cardiac home event monitor. Discussion: BAH is a life-threatening condition that should be promptly identified and managed in patients presenting with nonspecific symptoms and a history of hypercoagulability or anticoagulation. In these cases, the risk of AH and subsequent adrenal insufficiency is drastically increased, so immediate imaging as well as initiation of steroid therapy is crucial to stabilize patients and prevent adrenal crisis. A multidisciplinary approach, involving endocrinology, hematology, and cardiology as in this case is also imperative to optimize patient outcomes and increase survival. Conclusion: BAH should be considered in patients presenting with a history of VTE and hypercoagulable state when precipitating stressors or predisposing risk factors are present. This case report highlights the importance of clinical awareness of BAH for clinicians to accurately identify and manage it to prevent fatal sequelae and ensure long-term favorable patient outcomes.展开更多
BACKGROUND:Intracranial hemorrhage (ICH),a severe complication among adults receiving extracorporeal membrane oxygenation (ECMO),is often related to poor outcomes.This study aimed to establish a predictive model for I...BACKGROUND:Intracranial hemorrhage (ICH),a severe complication among adults receiving extracorporeal membrane oxygenation (ECMO),is often related to poor outcomes.This study aimed to establish a predictive model for ICH in adults receiving ECMO treatment.METHODS:Adults who received ECMO between January 2017 and June 2022 were the subjects of a single-center retrospective study.Patients under the age of 18 years old,with acute ICH before ECMO,with less than 24 h of ECMO support,and with incomplete data were excluded.ICH was diagnosed by a head computed tomography scan.The outcomes included the incidence of ICH,in-hosptial mortality and 28-day mortality.Multivariate logistic regression analysis was used to identify relevant risk factors of ICH,and a predictive model of ICH with a nomogram was constructed.RESULTS:Among the 227 patients included,22 developed ICH during ECMO.Patients with ICH had higher in-hospital mortality (90.9%vs.47.8%,P=0.001) and higher 28-day mortality (81.8%vs.47.3%,P=0.001) than patients with non-ICH.ICH was associated with decreased grey-white-matter ratio (GWR)(OR=0.894,95%CI:0.841–0.951,P<0.001),stroke history (OR=4.265,95%CI:1.052–17.291,P=0.042),fresh frozen plasma (FFP) transfusion (OR=1.208,95%CI:1.037–1.408,P=0.015)and minimum platelet (PLT) count during ECMO support (OR=0.977,95%CI:0.958–0.996,P=0.019).The area under the receiver operating characteristic curve of the ICH predictive model was 0.843 (95%CI:0.762–0.924,P<0.001).CONCLUSION:ECMO-treated patients with ICH had a higher risk of death.GWR,stroke history,FFP transfusion,and the minimum PLT count were independently associated with ICH,and the ICH predictive model showed that these parameters performed well as diagnostic tools.展开更多
BACKGROUND At present,the conventional methods for diagnosing cerebral edema in clinical practice are computed tomography(CT)and magnetic resonance imaging(MRI),which can evaluate the location and degree of peripheral...BACKGROUND At present,the conventional methods for diagnosing cerebral edema in clinical practice are computed tomography(CT)and magnetic resonance imaging(MRI),which can evaluate the location and degree of peripheral cerebral edema,but cannot realize quantification.When patients have symptoms of diffuse cerebral edema or high cranial pressure,CT or MRI often suggests that cerebral edema is lagging and cannot be dynamically monitored in real time.Intracranial pressure monitoring is the gold standard,but it is an invasive operation with high cost and complications.For clinical purposes,the ideal cerebral edema monitoring should be non-invasive,real-time,bedside,and continuous dynamic monitoring.The dis-turbance coefficient(DC)was used in this study to dynamically monitor the occu-rrence,development,and evolution of cerebral edema in patients with cerebral hemorrhage in real time,and review head CT or MRI to evaluate the development of the disease and guide further treatment,so as to improve the prognosis of patients with cerebral hemorrhage.AIM To offer a promising new approach for non-invasive adjuvant therapy in cerebral edema treatment.METHODS A total of 160 patients with hypertensive cerebral hemorrhage admitted to the Department of Neurosurgery,Second Affiliated Hospital of Xi’an Medical University from September 2018 to September 2019 were recruited.The patients were randomly divided into a control group(n=80)and an experimental group(n=80).Patients in the control group received conventional empirical treatment,while those in the experimental group were treated with mannitol dehydration under the guidance of DC.Subsequently,we compared the two groups with regards to the total dosage of mannitol,the total course of treatment,the incidence of complications,and prognosis.RESULTS The mean daily consumption of mannitol,the total course of treatment,and the mean hospitalization days were 362.7±117.7 mL,14.8±5.2 days,and 29.4±7.9 in the control group and 283.1±93.6 mL,11.8±4.2 days,and 23.9±8.3 in the experimental group(P<0.05).In the control group,there were 20 patients with pulmonary infection(25%),30 with electrolyte disturbance(37.5%),20 with renal impairment(25%),and 16 with stress ulcer(20%).In the experimental group,pulmonary infection occurred in 18 patients(22.5%),electrolyte disturbance in 6(7.5%),renal impairment in 2(2.5%),and stress ulcers in 15(18.8%)(P<0.05).According to the Glasgow coma scale score 6 months after discharge,the prognosis of the control group was good in 20 patients(25%),fair in 26(32.5%),and poor in 34(42.5%);the prognosis of the experimental group was good in 32(40%),fair in 36(45%),and poor in 12(15%)(P<0.05).CONCLUSION Using DC for non-invasive dynamic monitoring of cerebral edema demonstrates considerable clinical potential.It reduces mannitol dosage,treatment duration,complication rates,and hospital stays,ultimately lowering hospital-ization costs.Additionally,it improves overall patient prognosis,offering a promising new approach for non-invasive adjuvant therapy in cerebral edema treatment.展开更多
BACKGROUND Drug-induced lung injury is a common adverse effect of chemotherapeutic agents.Diffuse alveolar hemorrhage(DAH)is a fatal complication associated with druginduced lung injury.Early diagnosis and treatment o...BACKGROUND Drug-induced lung injury is a common adverse effect of chemotherapeutic agents.Diffuse alveolar hemorrhage(DAH)is a fatal complication associated with druginduced lung injury.Early diagnosis and treatment of DAH is critical,as delayed management can lead to respiratory failure and poor outcomes.However,the diagnosis of DAH is difficult because of the nonspecific clinical manifestations;as such,bronchoscopy is necessary to establish a diagnosis.CASE SUMMARY The patient presented with fever and dry cough.He had been receiving fluoropyrimidine and oxaliplatin therapy for esophageal squamous cell carcinoma.Chest imaging revealed diffuse ground-glass opacities.Bronchoscopy with bronchoalveolar lavage was performed,which confirmed the diagnosis of DAH.Although the patient’s respiratory status rapidly worsened,high-dose corticosteroid therapy with respiratory support gradually improved the patient’s condition and he was successfully extubated.CONCLUSION Prompt DAH diagnosis and bronchoscopy in patients receiving oxaliplatincontaining chemotherapy presenting with acute respiratory failure are critical for improving outcomes.展开更多
AIM:To elucidate the neuropathological mechanisms underlying diabetic vitreous hemorrhage(DVH)and its correlation with clinical characteristics.METHODS:Twenty-one individuals with DVH(male/female 12/9;mean age 52.29&#...AIM:To elucidate the neuropathological mechanisms underlying diabetic vitreous hemorrhage(DVH)and its correlation with clinical characteristics.METHODS:Twenty-one individuals with DVH(male/female 12/9;mean age 52.29±11.66y)were selected,alongside 21 appropriately matched controls with diabetes mellitus(DM).Voxel-based morphometry(VBM)techniques were employed to identify aberrant functional regions in the brain.Receiver operating characteristic(ROC)curves were utilized for classification based on the average VBM values of the two groups,and Pearson correlation analysis was conducted to assess the relationship between average VBM values in distinct brain regions and clinical manifestations.RESULTS:Relative to the DM controls,DVH patients exhibited reduced VBM values in the right superior temporal pole,the right superior temporal gyrus,the right medial orbital frontal gyrus,and the left superior frontal gyrus.Furthermore,ROC curve analysis of these four brain regions in DVH patients demonstrated a high degree of accuracy,as indicated by the area under the curve.The average VBM value in each of these regions exhibited a negative correlation with both the duration of DVH and the score on the Hospital Anxiety and Depression Scale(HADS).CONCLUSION:Pathological alterations in four distinct brain regions are observed in patients with DVH,potentially reflecting neuropathological changes associated with this condition.展开更多
Spontaneous intracerebral hemorrhage (ICH) accounts for one fifth of all strokes and is associated with an extremely high rate of morbidity and mortality. Affecting greater than 1 million people a year, ICH will leave...Spontaneous intracerebral hemorrhage (ICH) accounts for one fifth of all strokes and is associated with an extremely high rate of morbidity and mortality. Affecting greater than 1 million people a year, ICH will leave the majority of its’ patients significantly disabled or dead. An initially high systolic blood pressure upon presentation is associated with hematoma expansion, peri-hema- toma expansion, and increased mortality. The relationship between blood pressure, the degree of blood pressure control and hematoma expansion has yet to be defined, but the literature has ob- served a relationship between tightly controlled blood pressures and decreased hematoma expansion. There have been many proposed mechanisms to explain this effect. Larger initial hematomas may lend greater hydrostatic forces and this could result in greater total hematoma volume, and greater surrounding edema. Recent literature has suggested that blood pressure reductions in acute ICH may be tolerated because of reduced metabolism, and preserved autoreguation in the peri-hematoma region. The volume of the hematoma is a critical determinant of mortality and functional outcome after intracerebral hemorrhage, and early hematoma growth is an important cause of neurologic deterioration. An increase in volume of more than thirty-three percent is detectable on repeated computed tomography (CT) in thirty-eight percent of patients initially scanned within the first three hours of onset of symptoms;in two thirds of these cases this change is noticeable on CT within the first hour. This supports the hypothesis that early aggressive blood pressure optimization would decrease hematoma size and edema. This is further supported by the fact that patients with high blood pressure and acute intracerebral hemorrhage have worse outcomes than their counterparts. We hypothesize that prompt and aggressive, early blood pressure reduction in emergency department patients with acute spontaneous intracerebral hemorrhage will result in a reduction of early hematoma growth. The study institution is a large urban emergency department and tertiary care stoke center, with over 55,000 emergency department visits per year. This prospective cohort study compared the results and outcomes observed within the enrolled prospective study population, to the results and outcomes of a matched historical cohort population (future patients with intracranial hemorrhage that did not receive the ABC-ICH protocol). Methods and Material: A nicardipine infusion was administered to optimize blood pressure in all patients presenting with intracerebral hemorrhage with a target mean arterial pressure (MAP) of 80 - 110. Hematoma volume (primary outcome measure) was measured on cat scans at time of presentation and at twenty-four hours. The hematoma volume in the enrolled prospective study population was compared to those of a matched cohort (patients with intracranial hemorrhage that did not receive the ABC-ICH protocol following the conclusion of the study). Results: One hundred total patients were enrolled into the study. Fifty patients were enrolled prospectively in the study and matched to a similar group of fifty cohort patients. The difference in the mean change of hematoma volume at twenty-four hours was 7.29 ml (control) and 2.84 ml (study). The result was an absolute decrease in hematoma size of 4.45 ml in the group treated aggressively with nicardapine for blood pressure reduction within one hour of their initial presentation. Conclusions: These results support the previous research suggesting that aggressive blood pressure control in intracerebral hemorrhage reduces hematoma growth, however the clinical benefit of such a reduction will have to be evaluated in ongoing research.展开更多
基金supported by the National Natural Science Foundation of China,No.82072110Suzhou Municipal Science and Technology Bureau,No.SKJY2021046+1 种基金Shanghai Key Lab of Forensic Medicine&Key Lab of Forensic Science,Ministry of Justice,China(Academy of Forensic Science),No.KF202201a Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD)(all to TW).
文摘Cholesterol is an important component of plasma membranes and participates in many basic life functions,such as the maintenance of cell membrane stability,the synthesis of steroid hormones,and myelination.Cholesterol plays a key role in the establishment and maintenance of the central nervous system.The brain contains 20%of the whole body’s cholesterol,80%of which is located within myelin.A huge number of processes(e.g.,the sterol regulatory element-binding protein pathway and liver X receptor pathway)participate in the regulation of cholesterol metabolism in the brain via mechanisms that include cholesterol biosynthesis,intracellular transport,and efflux.Certain brain injuries or diseases involving crosstalk among the processes above can affect normal cholesterol metabolism to induce detrimental consequences.Therefore,we hypothesized that cholesterol-related molecules and pathways can serve as therapeutic targets for central nervous system diseases.Intracerebral hemorrhage is the most severe hemorrhagic stroke subtype,with high mortality and morbidity.Historical cholesterol levels are associated with the risk of intracerebral hemorrhage.Moreover,secondary pathological changes after intracerebral hemorrhage are associated with cholesterol metabolism dysregulation,such as neuroinflammation,demyelination,and multiple types of programmed cell death.Intracellular cholesterol accumulation in the brain has been found after intracerebral hemorrhage.In this paper,we review normal cholesterol metabolism in the central nervous system,the mechanisms known to participate in the disturbance of cholesterol metabolism after intracerebral hemorrhage,and the links between cholesterol metabolism and cell death.We also review several possible and constructive therapeutic targets identified based on cholesterol metabolism to provide cholesterol-based perspectives and a reference for those interested in the treatment of intracerebral hemorrhage.
文摘In the article titled“Neuroprotection mediated by the Wnt/Frizzled signaling pathway in early brain injury induced by subarachnoid hemorrhage,”published on pages 1013-1024,Issue 6,Volume 14 of Neural Regeneration Research(Wang et al.,2019),there are some errors in selecting the appropriate images in Figures 4A,4B,and 5A by authors during assembling the images.
文摘In this article,we comment on the paper by Kakinuma et al published recently.We focus specifically on the diagnosis of uterine pseudoaneurysm,but we also review other uterine vascular anomalies that may be the cause of life-threating hemorrhage and the different causes of uterine pseudoaneurysms.Uterine artery pseudoaneurysm is a complication of both surgical gynecological and nontraumatic procedures.Massive hemorrhage is the consequence of the rupture of the pseudoaneurysm.Uterine artery pseudoaneurysm can develop after obstetric or gynecological procedures,being the most frequent after cesarean or vaginal deliveries,curettage and even during pregnancy.However,there are several cases described unrelated to pregnancy,such as after conization,hysteroscopic surgery or laparoscopic myomectomy.Hemorrhage is the clinical manifestation and it can be life-threatening so suspicion of this vascular lesion is essential for early diagnosis and treatment.However,there are other uterine vascular anomalies that may be the cause of severe hemorrhage,which must be taken into account in the differential diagnosis.Computed tomography angiography and embolization is supposed to be the first therapeutic option in most of them.
基金funded by Taiju Life Social Welfare Foundation(to HS).
文摘Aneurysm rupture can result in subarachnoid hemorrhage,a condition with potentially severe consequences,such as disability and death.In the acute stage,early brain injury manifests as intracranial pressure elevation,global cerebral ischemia,acute hydrocephalus,and direct blood–brain contact due to aneurysm rupture.This may subsequently cause delayed cerebral infarction,often with cerebral vasospasm,significantly affecting patient outcomes.Chronic complications such as brain volume loss and chronic hydrocephalus can further impact outcomes.Investigating the mechanisms of subarachnoid hemorrhage-induced brain injury is paramount for identifying effective treatments.Stem cell therapy,with its multipotent differentiation capacity and anti-inflammatory effects,has emerged as a promising approach for treating previously deemed incurable conditions.This review focuses on the potential application of stem cells in subarachnoid hemorrhage pathology and explores their role in neurogenesis and as a therapeutic intervention in preclinical and clinical subarachnoid hemorrhage studies.
基金supported by the Natural Science Foundation of Shandong Province,No.ZR2022MH124the Youth Science Foundation of Shandong First Medical University,No.202201–105(both to YX)。
文摘Subarachnoid hemorrhage leads to a series of pathological changes,including vascular spasm,cellular apoptosis,blood–brain barrier damage,cerebral edema,and white matter injury.Microglia,which are the key immune cells in the central nervous system,maintain homeostasis in the neural environment,support neurons,mediate apoptosis,participate in immune regulation,and have neuroprotective effects.Increasing evidence has shown that microglia play a pivotal role in the pathogenesis of subarachnoid hemorrhage and affect the process of injury and the prognosis of subarachnoid hemorrhage.Moreover,microglia play certain neuroprotective roles in the recovery phase of subarachnoid hemorrhage.Several approaches aimed at modulating microglia function are believed to attenuate subarachnoid hemorrhage injury.This provides new targets and ideas for the treatment of subarachnoid hemorrhage.However,an in-depth and comprehensive summary of the role of microglia after subarachnoid hemorrhage is still lacking.This review describes the activation of microglia after subarachnoid hemorrhage and their roles in the pathological processes of vasospasm,neuroinflammation,neuronal apoptosis,blood–brain barrier disruption,cerebral edema,and cerebral white matter lesions.It also discusses the neuroprotective roles of microglia during recovery from subarachnoid hemorrhage and therapeutic advances aimed at modulating microglial function after subarachnoid hemorrhage.Currently,microglia in subarachnoid hemorrhage are targeted with TLR inhibitors,nuclear factor-κB and STAT3 pathway inhibitors,glycine/tyrosine kinases,NLRP3 signaling pathway inhibitors,Gasdermin D inhibitors,vincristine receptorαreceptor agonists,ferroptosis inhibitors,genetic modification techniques,stem cell therapies,and traditional Chinese medicine.However,most of these are still being evaluated at the laboratory stage.More clinical studies and data on subarachnoid hemorrhage are required to improve the treatment of subarachnoid hemorrhage.
基金supported by the National Natural Science Foundation of China,No.8227050826(to PL)Tianjin Science and Technology Bureau Foundation,No.20201194(to PL)Tianjin Graduate Research and Innovation Project,No.2022BKY174(to CW).
文摘Cerebral edema caused by blood-brain barrier injury after intracerebral hemorrhage is an important factor leading to poor prognosis.Human-induced pluripotent stem cell-derived neural stem cell exosomes(hiPSC-NSC-Exos)have shown potential for brain injury repair in central nervous system diseases.In this study,we explored the impact of hiPSC-NSC-Exos on blood-brain barrier preservation and the underlying mechanism.Our results indicated that intranasal delivery of hiPSC-NSC-Exos mitigated neurological deficits,enhanced blood-brain barrier integrity,and reduced leukocyte infiltration in a mouse model of intracerebral hemorrhage.Additionally,hiPSC-NSC-Exos decreased immune cell infiltration,activated astrocytes,and decreased the secretion of inflammatory cytokines like monocyte chemoattractant protein-1,macrophage inflammatory protein-1α,and tumor necrosis factor-αpost-intracerebral hemorrhage,thereby improving the inflammatory microenvironment.RNA sequencing indicated that hiPSC-NSC-Exo activated the PI3K/AKT signaling pathway in astrocytes and decreased monocyte chemoattractant protein-1 secretion,thereby improving blood-brain barrier integrity.Treatment with the PI3K/AKT inhibitor LY294002 or the monocyte chemoattractant protein-1 neutralizing agent C1142 abolished these effects.In summary,our findings suggest that hiPSC-NSC-Exos maintains blood-brain barrier integrity,in part by downregulating monocyte chemoattractant protein-1 secretion through activation of the PI3K/AKT signaling pathway in astrocytes.
基金Supported by Shanxi Provincial Key Research and Development Plan Project,No.2020ZDLSF01-02Doctor Foundation of the Second Affiliated Hospital of Xi’an Medical University,No.X2Y-R11.
文摘Intracerebral hemorrhage(ICH)is a common severe emergency in neurosurgery,causing tremendous economic pressure on families and society and devastating effects on patients both physically and psychologically,especially among patients with poor functional outcomes.ICH is often accompanied by decreased consciousness and limb dysfunction.This seriously affects patients’ability to live independently.Although rapid advances in neurosurgery have greatly improved patient survival,there remains insufficient evidence that surgical treatment significantly improves long-term outcomes.With in-depth pathophysiological studies after ICH,increasing evidence has shown that secondary injury after ICH is related to long-term prognosis and that the key to secondary injury is various immune-mediated neuroinflammatory reactions after ICH.In basic and clinical studies of various systemic inflammatory diseases,triggering receptor expressed on myeloid cells 1/2(TREM-1/2),and the TREM receptor family is closely related to the inflammatory response.Various inflammatory diseases can be upregulated and downregulated through receptor intervention.How the TREM receptor functions after ICH,the types of results from intervention,and whether the outcomes can improve secondary brain injury and the long-term prognosis of patients are unknown.An analysis of relevant research results from basic and clinical trials revealed that the inhibition of TREM-1 and the activation of TREM-2 can alleviate the neuroinflammatory immune response,significantly improve the long-term prognosis of neurological function in patients with cerebral hemorrhage,and thus improve the ability of patients to live independently.
文摘Background: Bilateral adrenal hemorrhage (BAH) is a rare condition that may lead to life-threatening adrenal insufficiency or adrenal crisis if not addressed appropriately. Case Report: A 54-year-old male with a history of venous thromboembolism (VTE) on warfarin presented to the hospital with nausea, vomiting, and abdominal and flank pain shortly following colonoscopy preparation. Initial imaging of the abdomen and pelvis was notable for hyperdense thickening of the bilateral adrenal glands raising concerns for hemorrhages, and subsequent magnetic resonance imaging (MRI) confirmed BAH. During hospitalization, the patient was placed on prophylactic heparin, and shortly after decompensating, he became tachycardic, hypotensive, and febrile. This led to heparin reversal followed by administration of a single dose of Hydrocortisone 100 mg and Hydrocortisone 50 mg TID due to concern for adrenal insufficiency. The patient also necessitated sepsis work-up and fluid resuscitation. Repeat CT imaging showed no significant change in hemorrhage size bilaterally. Endocrinology, vascular surgery, hematology/oncology, and rheumatology were consulted for the management of adrenal insufficiency, anticoagulation in the presence of hemorrhage, thrombocytopenia, and hypercoagulable state. Towards the end of his hospital course, the patient had asymptomatic diffuse ST elevations, elevated troponin, and an ejection fraction of 10% - 15%, leading to cardiac catheterization and placement of an intra-aortic pump. During subsequent stay in the ICU, the patient developed hemodynamic shock and was transferred to a facility with a higher level of care and medical support therapies. After this transfer, the patient was stabilized from a cardiac standpoint but developed acute respiratory failure suspected to be secondary to diffuse alveolar hemorrhage and immune thrombocytopenic purpura, necessitating platelet transfusion. He was on continued monitoring from rheumatology given his myocarditis believed to be secondary to his antiphospholipid antibodies, and was treated with IVIG, rituximab, and hydroxychloroquine. A repeat echocardiogram revealed an improved ejection fraction of 52% and the patient was then discharged on an enoxaparin bridge to warfarin and a cardiac home event monitor. Discussion: BAH is a life-threatening condition that should be promptly identified and managed in patients presenting with nonspecific symptoms and a history of hypercoagulability or anticoagulation. In these cases, the risk of AH and subsequent adrenal insufficiency is drastically increased, so immediate imaging as well as initiation of steroid therapy is crucial to stabilize patients and prevent adrenal crisis. A multidisciplinary approach, involving endocrinology, hematology, and cardiology as in this case is also imperative to optimize patient outcomes and increase survival. Conclusion: BAH should be considered in patients presenting with a history of VTE and hypercoagulable state when precipitating stressors or predisposing risk factors are present. This case report highlights the importance of clinical awareness of BAH for clinicians to accurately identify and manage it to prevent fatal sequelae and ensure long-term favorable patient outcomes.
基金supported by the National Natural Science Foundation of China (82072159)。
文摘BACKGROUND:Intracranial hemorrhage (ICH),a severe complication among adults receiving extracorporeal membrane oxygenation (ECMO),is often related to poor outcomes.This study aimed to establish a predictive model for ICH in adults receiving ECMO treatment.METHODS:Adults who received ECMO between January 2017 and June 2022 were the subjects of a single-center retrospective study.Patients under the age of 18 years old,with acute ICH before ECMO,with less than 24 h of ECMO support,and with incomplete data were excluded.ICH was diagnosed by a head computed tomography scan.The outcomes included the incidence of ICH,in-hosptial mortality and 28-day mortality.Multivariate logistic regression analysis was used to identify relevant risk factors of ICH,and a predictive model of ICH with a nomogram was constructed.RESULTS:Among the 227 patients included,22 developed ICH during ECMO.Patients with ICH had higher in-hospital mortality (90.9%vs.47.8%,P=0.001) and higher 28-day mortality (81.8%vs.47.3%,P=0.001) than patients with non-ICH.ICH was associated with decreased grey-white-matter ratio (GWR)(OR=0.894,95%CI:0.841–0.951,P<0.001),stroke history (OR=4.265,95%CI:1.052–17.291,P=0.042),fresh frozen plasma (FFP) transfusion (OR=1.208,95%CI:1.037–1.408,P=0.015)and minimum platelet (PLT) count during ECMO support (OR=0.977,95%CI:0.958–0.996,P=0.019).The area under the receiver operating characteristic curve of the ICH predictive model was 0.843 (95%CI:0.762–0.924,P<0.001).CONCLUSION:ECMO-treated patients with ICH had a higher risk of death.GWR,stroke history,FFP transfusion,and the minimum PLT count were independently associated with ICH,and the ICH predictive model showed that these parameters performed well as diagnostic tools.
基金Supported by the Shaanxi Provincial Key Research and Development Plan Project,No.2020ZDLSF01-02.
文摘BACKGROUND At present,the conventional methods for diagnosing cerebral edema in clinical practice are computed tomography(CT)and magnetic resonance imaging(MRI),which can evaluate the location and degree of peripheral cerebral edema,but cannot realize quantification.When patients have symptoms of diffuse cerebral edema or high cranial pressure,CT or MRI often suggests that cerebral edema is lagging and cannot be dynamically monitored in real time.Intracranial pressure monitoring is the gold standard,but it is an invasive operation with high cost and complications.For clinical purposes,the ideal cerebral edema monitoring should be non-invasive,real-time,bedside,and continuous dynamic monitoring.The dis-turbance coefficient(DC)was used in this study to dynamically monitor the occu-rrence,development,and evolution of cerebral edema in patients with cerebral hemorrhage in real time,and review head CT or MRI to evaluate the development of the disease and guide further treatment,so as to improve the prognosis of patients with cerebral hemorrhage.AIM To offer a promising new approach for non-invasive adjuvant therapy in cerebral edema treatment.METHODS A total of 160 patients with hypertensive cerebral hemorrhage admitted to the Department of Neurosurgery,Second Affiliated Hospital of Xi’an Medical University from September 2018 to September 2019 were recruited.The patients were randomly divided into a control group(n=80)and an experimental group(n=80).Patients in the control group received conventional empirical treatment,while those in the experimental group were treated with mannitol dehydration under the guidance of DC.Subsequently,we compared the two groups with regards to the total dosage of mannitol,the total course of treatment,the incidence of complications,and prognosis.RESULTS The mean daily consumption of mannitol,the total course of treatment,and the mean hospitalization days were 362.7±117.7 mL,14.8±5.2 days,and 29.4±7.9 in the control group and 283.1±93.6 mL,11.8±4.2 days,and 23.9±8.3 in the experimental group(P<0.05).In the control group,there were 20 patients with pulmonary infection(25%),30 with electrolyte disturbance(37.5%),20 with renal impairment(25%),and 16 with stress ulcer(20%).In the experimental group,pulmonary infection occurred in 18 patients(22.5%),electrolyte disturbance in 6(7.5%),renal impairment in 2(2.5%),and stress ulcers in 15(18.8%)(P<0.05).According to the Glasgow coma scale score 6 months after discharge,the prognosis of the control group was good in 20 patients(25%),fair in 26(32.5%),and poor in 34(42.5%);the prognosis of the experimental group was good in 32(40%),fair in 36(45%),and poor in 12(15%)(P<0.05).CONCLUSION Using DC for non-invasive dynamic monitoring of cerebral edema demonstrates considerable clinical potential.It reduces mannitol dosage,treatment duration,complication rates,and hospital stays,ultimately lowering hospital-ization costs.Additionally,it improves overall patient prognosis,offering a promising new approach for non-invasive adjuvant therapy in cerebral edema treatment.
文摘BACKGROUND Drug-induced lung injury is a common adverse effect of chemotherapeutic agents.Diffuse alveolar hemorrhage(DAH)is a fatal complication associated with druginduced lung injury.Early diagnosis and treatment of DAH is critical,as delayed management can lead to respiratory failure and poor outcomes.However,the diagnosis of DAH is difficult because of the nonspecific clinical manifestations;as such,bronchoscopy is necessary to establish a diagnosis.CASE SUMMARY The patient presented with fever and dry cough.He had been receiving fluoropyrimidine and oxaliplatin therapy for esophageal squamous cell carcinoma.Chest imaging revealed diffuse ground-glass opacities.Bronchoscopy with bronchoalveolar lavage was performed,which confirmed the diagnosis of DAH.Although the patient’s respiratory status rapidly worsened,high-dose corticosteroid therapy with respiratory support gradually improved the patient’s condition and he was successfully extubated.CONCLUSION Prompt DAH diagnosis and bronchoscopy in patients receiving oxaliplatincontaining chemotherapy presenting with acute respiratory failure are critical for improving outcomes.
基金Supported by National Natural Science Foundation of China(No.82160195,No.82460203)Science and Technology Project of Jiangxi Provincial Department of Education(No.GJJ200169)+1 种基金Science and Technology Project of Jiangxi Province Health Commission of Traditional Chinese Medicine(No.2020A0087)Science and Technology Project of Jiangxi Health Commission(No.202130210).
文摘AIM:To elucidate the neuropathological mechanisms underlying diabetic vitreous hemorrhage(DVH)and its correlation with clinical characteristics.METHODS:Twenty-one individuals with DVH(male/female 12/9;mean age 52.29±11.66y)were selected,alongside 21 appropriately matched controls with diabetes mellitus(DM).Voxel-based morphometry(VBM)techniques were employed to identify aberrant functional regions in the brain.Receiver operating characteristic(ROC)curves were utilized for classification based on the average VBM values of the two groups,and Pearson correlation analysis was conducted to assess the relationship between average VBM values in distinct brain regions and clinical manifestations.RESULTS:Relative to the DM controls,DVH patients exhibited reduced VBM values in the right superior temporal pole,the right superior temporal gyrus,the right medial orbital frontal gyrus,and the left superior frontal gyrus.Furthermore,ROC curve analysis of these four brain regions in DVH patients demonstrated a high degree of accuracy,as indicated by the area under the curve.The average VBM value in each of these regions exhibited a negative correlation with both the duration of DVH and the score on the Hospital Anxiety and Depression Scale(HADS).CONCLUSION:Pathological alterations in four distinct brain regions are observed in patients with DVH,potentially reflecting neuropathological changes associated with this condition.
文摘Spontaneous intracerebral hemorrhage (ICH) accounts for one fifth of all strokes and is associated with an extremely high rate of morbidity and mortality. Affecting greater than 1 million people a year, ICH will leave the majority of its’ patients significantly disabled or dead. An initially high systolic blood pressure upon presentation is associated with hematoma expansion, peri-hema- toma expansion, and increased mortality. The relationship between blood pressure, the degree of blood pressure control and hematoma expansion has yet to be defined, but the literature has ob- served a relationship between tightly controlled blood pressures and decreased hematoma expansion. There have been many proposed mechanisms to explain this effect. Larger initial hematomas may lend greater hydrostatic forces and this could result in greater total hematoma volume, and greater surrounding edema. Recent literature has suggested that blood pressure reductions in acute ICH may be tolerated because of reduced metabolism, and preserved autoreguation in the peri-hematoma region. The volume of the hematoma is a critical determinant of mortality and functional outcome after intracerebral hemorrhage, and early hematoma growth is an important cause of neurologic deterioration. An increase in volume of more than thirty-three percent is detectable on repeated computed tomography (CT) in thirty-eight percent of patients initially scanned within the first three hours of onset of symptoms;in two thirds of these cases this change is noticeable on CT within the first hour. This supports the hypothesis that early aggressive blood pressure optimization would decrease hematoma size and edema. This is further supported by the fact that patients with high blood pressure and acute intracerebral hemorrhage have worse outcomes than their counterparts. We hypothesize that prompt and aggressive, early blood pressure reduction in emergency department patients with acute spontaneous intracerebral hemorrhage will result in a reduction of early hematoma growth. The study institution is a large urban emergency department and tertiary care stoke center, with over 55,000 emergency department visits per year. This prospective cohort study compared the results and outcomes observed within the enrolled prospective study population, to the results and outcomes of a matched historical cohort population (future patients with intracranial hemorrhage that did not receive the ABC-ICH protocol). Methods and Material: A nicardipine infusion was administered to optimize blood pressure in all patients presenting with intracerebral hemorrhage with a target mean arterial pressure (MAP) of 80 - 110. Hematoma volume (primary outcome measure) was measured on cat scans at time of presentation and at twenty-four hours. The hematoma volume in the enrolled prospective study population was compared to those of a matched cohort (patients with intracranial hemorrhage that did not receive the ABC-ICH protocol following the conclusion of the study). Results: One hundred total patients were enrolled into the study. Fifty patients were enrolled prospectively in the study and matched to a similar group of fifty cohort patients. The difference in the mean change of hematoma volume at twenty-four hours was 7.29 ml (control) and 2.84 ml (study). The result was an absolute decrease in hematoma size of 4.45 ml in the group treated aggressively with nicardapine for blood pressure reduction within one hour of their initial presentation. Conclusions: These results support the previous research suggesting that aggressive blood pressure control in intracerebral hemorrhage reduces hematoma growth, however the clinical benefit of such a reduction will have to be evaluated in ongoing research.
