Objective To evaluate the utility of computed tomography perfusion(CTP)both at admission and during delayed cerebral ischemia time-window(DCITW)in the detection of delayed cerebral ischemia(DCI)and the change in CTP p...Objective To evaluate the utility of computed tomography perfusion(CTP)both at admission and during delayed cerebral ischemia time-window(DCITW)in the detection of delayed cerebral ischemia(DCI)and the change in CTP parameters from admission to DCITW following aneurysmal subarachnoid hemorrhage.Methods Eighty patients underwent CTP at admission and during DCITW.The mean and extreme values of all CTP parameters at admission and during DCITW were compared between the DCI group and non-DCI group,and comparisons were also made between admission and DCITW within each group.The qualitative color-coded perfusion maps were recorded.Finally,the relationship between CTP parameters and DCI was assessed by receiver operating characteristic(ROC)analyses.Results With the exception of cerebral blood volume(P=0.295,admission;P=0.682,DCITW),there were significant differences in the mean quantitative CTP parameters between DCI and non-DCI patients both at admission and during DCITW.In the DCI group,the extreme parameters were significantly different between admission and DCITW.The DCI group also showed a deteriorative trend in the qualitative color-coded perfusion maps.For the detection of DCI,mean transit time to the center of the impulse response function(Tmax)at admission and mean time to start(TTS)during DCITW had the largest area under curve(AUC),0.698 and 0.789,respectively.Conclusion Whole-brain CTP can predict the occurrence of DCI at admission and diagnose DCI during DCITW.The extreme quantitative parameters and qualitative color-coded perfusion maps can better reflect the perfusion changes of patients with DCI from admission to DCITW.展开更多
Background:Dysfunction of cerebral autoregulation is one of the pathophysiological mechanisms that causes delayed cerebral ischemia(DCI)after subarachnoid hemorrhage(SAH).Pressure reactivity index(PRx)have been confir...Background:Dysfunction of cerebral autoregulation is one of the pathophysiological mechanisms that causes delayed cerebral ischemia(DCI)after subarachnoid hemorrhage(SAH).Pressure reactivity index(PRx)have been confirmed to reflect the level of cerebral autoregulation and used to derive optimal cerebral perfusion pressure(CPPopt).The goal of this study is to explore the associations between autoregulation,CPPopt,PRx,and DCI.Methods:Continuous intracranial pressure(ICP),arterial blood pressure(ABP),and cerebral perfusion pressure(CPP)signals acquired from 61 aSAH patients were retrospectively analyzed.PRx was calculated and collected by Pneumatic computer system.The CPP at the lowest PRx was determined as the CPPopt.The duration of a hypoperfusion event(dHP)was defined as the cumulative time that the PRx was>0.3 and the CPP was<CPPopt.The duration of CPP more than 10 mmHg below CPPopt(ΔCPPopt<−10 mmHg)was also used to assess hypoperfusion.The percent of the time of hypoperfusion by dHP andΔCPPopt<−10 mmHg(%dHP and%ΔCPPopt)were compared between DCI group and control group,utilizing univariate and multivariable logistic regression.It was the clinical prognosis at 3 months after hemorrhage that was assessed with the modified Rankin Scale,and logistic regression and ROC analysis were used for predictive power for unfavorable outcomes(mRs 3–5).Results:Data from 52 patients were included in the final analysis of 61 patients.The mean%dHP in DCI was 29.23%and 10.66%in control.The mean%ΔCPPopt<−10 mmHg was 22.28%,and 5.90%in control.The%dHP(p<0.001)and the%ΔCPPopt<−10mmHg(p<0.001)was significantly longer in the DCI group.In multivariate logistic regression model,%ΔCPPopt<−10 mmHg(p<0.001)and%dHP(p<0.001)were independent risk factor for predicting DCI,and%ΔCPPopt<−10 mmHg(p=0.010)and%dHP(p=0.026)were independent risk factor for predicting unfavorable outcomes.Conclusions:The increase of duration of hypoperfusion events and duration of CPP below CPPopt over 10 mmHg,evaluated as time of lowered CPP,is highly indicative of DCI and unfavorable outcomes.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
Neuroinflammation is a well-recognized consequence of subarachnoid hemorrhage（SAH）, and Toll-like receptor（TLR） 4 may be an important therapeutic target for post-SAH neuroinflammation. Of the TLR family members, T...Neuroinflammation is a well-recognized consequence of subarachnoid hemorrhage（SAH）, and Toll-like receptor（TLR） 4 may be an important therapeutic target for post-SAH neuroinflammation. Of the TLR family members, TLR4 is expressed in various cell types in the central nervous system, and is unique in that it can signal through both the myeloid differentiation primary-response protein 88-dependent and the toll receptor associated activator of interferon-dependent cascades to coordinate the maximal inflammatory response. TLR4 can be activated by many endogenous ligands having damage-associated molecular patterns including heme and fibrinogen at the rupture of an intracranial aneurysm, and the resultant inflammatory reaction and thereby tissue damages may furthermore activate TLR4. It is widely accepted that the excreted products of TLR4 signaling alter neuronal functions. Previous studies have focused on the pathway through nuclear factor（NF）-κΒ signaling among TLR4 signaling pathways as to the development of early brain injury（EBI） such as neuronal apoptosis and blood-brain barrier disruption, and cerebral vasospasm. However, many findings suggest that both pathways via NF-κΒ and mitogen-activated protein kinases may be involved in EBI and cerebral vasospasm development. To overcome EBI and cerebral vasospasm is important to improve outcomes after SAH, because both EBI and vasopasm are responsible for delayed brain injuries or delayed cerebral ischemia, the most important preventable cause of poor outcomes after SAH. Increasing evidence has shown that TLR4 signaling plays an important role in SAH-induced brain injuries. Better understanding of the roles of TLR4 signaling in SAH will facilitate development of new treatments.展开更多
In this manuscript a comprehensive coverage of recent developments in the drug therapy of vasospasm while providing the background information that neuroscientists need to understand its rationale. The range of new ag...In this manuscript a comprehensive coverage of recent developments in the drug therapy of vasospasm while providing the background information that neuroscientists need to understand its rationale. The range of new agents available for treatment of cerebral vasospasm is expanding rapidly along with rapid advances in pharmacology and physiology that are uncovering the mechanisms of this disease. Although there are many publications for treatment of cerebral vaso-spasm, most are focusing on different aspects of vasospasm treatment and many have limited value due to insufficient quality. Moreover, the complexity of this, in many cases deleterious condition, is enormous and the information needed to understand drug effects is accordingly often not readily available in a single source. A number of pharmacological and medical therapies are currently in use or being investigated in an attempt to reverse cerebral vasospasm, but only a few have proven to be useful. Current research efforts promise the eventual production of new medical therapies. At last, recommendations for the use of different treatment stages based on currently available clinical data are provided.展开更多
Infusion of the colloid hydroxyethylstarch has been used for volume substitution to maintain hemodynamics and microcirculation after e.g., severe blood loss.In the last decade it was revealed that hydroxyethylstarch c...Infusion of the colloid hydroxyethylstarch has been used for volume substitution to maintain hemodynamics and microcirculation after e.g., severe blood loss.In the last decade it was revealed that hydroxyethylstarch can aggravate acute kidney injury, especially in septic patients.Because of the serious risk for critically ill patients, the administration of hydroxyethylstarch was restricted for clinical use.Animal studies and recently published in vitro experiments showed that hydroxyethylstarch might exert protective effects on the blood-brain barrier.Since the prevention of blood-brain barrier disruption was shown to go along with the reduction of brain damage after several kinds of insults, we revisit the topic hydroxyethylstarch and discuss a possible niche for the application of hydroxyethylstarch in acute brain injury treatment.展开更多
BACKGROUND:A20 may be a neuroprotective factor.Herein,we aimed to investigate whether serum A20 levels were associated with disease severity,delayed cerebral ischemia(DCI),and outcome after aneurysmal subarachnoid hem...BACKGROUND:A20 may be a neuroprotective factor.Herein,we aimed to investigate whether serum A20 levels were associated with disease severity,delayed cerebral ischemia(DCI),and outcome after aneurysmal subarachnoid hemorrhage(aSAH).METHODS:In this prospective cohort study containing 112 aSAH patients and 112 controls,serum A20 levels were quantified.At 90 d poststroke,Modified Rankin Scale(MRS) scores≥3 were defined as a poor outcome.All correlations and associations were assessed using multivariate analysis.RESULTS:Compared with controls,there was a significant elevation of serum A20 levels in patients(median 123.7 pg/mL vs.25.8 pg/mL;P<0.001).Serum A20 levels were independently correlated with Hunt-Hess scores(β 9.854;95% confidence interval [95% CI] 2.481-17.227,P=0.009) and modified Fisher scores(β 10.349,95% CI 1.273-19.424,P=0.026).Independent associations were found between serum A20 levels and poor outcome(odds ratio [OR] 1.015,95%CI 1.000-1.031,P=0.047) and DCI(OR 1.018,95% CI 1.001-1.035,P=0.042).Areas under the curve for predicting poor outcome and DCI were 0.771(95% CI 0.682-0.845) and 0.777(95% CI 0.688-0.850),respectively.Serum A20 levels ≥128.15 pg/mL predicted poor outcome,with a sensitivity of 73.9% and specificity of 74.2%,and A20 levels ≥160.55 pg/mL distinguished the risk of DCI with65.5% sensitivity and 89.2% specificity.Its ability to predict poor outcome and DCI was similar to those of Hunt-Hess scores and modified Fisher scores(both P>0.05).CONCLUSION:Enhanced serum A20 levels are significantly associated with stroke severity and poor clinical outcome after aSAH,implying that serum A20 may be a potential prognostic biomarker for aSAH.展开更多
基金supported by the National Natural Science Foundation of China,Research on Brain Magnetic Resonance Image Segmentation Based on Particle Computation(No.61672386).
文摘Objective To evaluate the utility of computed tomography perfusion(CTP)both at admission and during delayed cerebral ischemia time-window(DCITW)in the detection of delayed cerebral ischemia(DCI)and the change in CTP parameters from admission to DCITW following aneurysmal subarachnoid hemorrhage.Methods Eighty patients underwent CTP at admission and during DCITW.The mean and extreme values of all CTP parameters at admission and during DCITW were compared between the DCI group and non-DCI group,and comparisons were also made between admission and DCITW within each group.The qualitative color-coded perfusion maps were recorded.Finally,the relationship between CTP parameters and DCI was assessed by receiver operating characteristic(ROC)analyses.Results With the exception of cerebral blood volume(P=0.295,admission;P=0.682,DCITW),there were significant differences in the mean quantitative CTP parameters between DCI and non-DCI patients both at admission and during DCITW.In the DCI group,the extreme parameters were significantly different between admission and DCITW.The DCI group also showed a deteriorative trend in the qualitative color-coded perfusion maps.For the detection of DCI,mean transit time to the center of the impulse response function(Tmax)at admission and mean time to start(TTS)during DCITW had the largest area under curve(AUC),0.698 and 0.789,respectively.Conclusion Whole-brain CTP can predict the occurrence of DCI at admission and diagnose DCI during DCITW.The extreme quantitative parameters and qualitative color-coded perfusion maps can better reflect the perfusion changes of patients with DCI from admission to DCITW.
文摘Background:Dysfunction of cerebral autoregulation is one of the pathophysiological mechanisms that causes delayed cerebral ischemia(DCI)after subarachnoid hemorrhage(SAH).Pressure reactivity index(PRx)have been confirmed to reflect the level of cerebral autoregulation and used to derive optimal cerebral perfusion pressure(CPPopt).The goal of this study is to explore the associations between autoregulation,CPPopt,PRx,and DCI.Methods:Continuous intracranial pressure(ICP),arterial blood pressure(ABP),and cerebral perfusion pressure(CPP)signals acquired from 61 aSAH patients were retrospectively analyzed.PRx was calculated and collected by Pneumatic computer system.The CPP at the lowest PRx was determined as the CPPopt.The duration of a hypoperfusion event(dHP)was defined as the cumulative time that the PRx was>0.3 and the CPP was<CPPopt.The duration of CPP more than 10 mmHg below CPPopt(ΔCPPopt<−10 mmHg)was also used to assess hypoperfusion.The percent of the time of hypoperfusion by dHP andΔCPPopt<−10 mmHg(%dHP and%ΔCPPopt)were compared between DCI group and control group,utilizing univariate and multivariable logistic regression.It was the clinical prognosis at 3 months after hemorrhage that was assessed with the modified Rankin Scale,and logistic regression and ROC analysis were used for predictive power for unfavorable outcomes(mRs 3–5).Results:Data from 52 patients were included in the final analysis of 61 patients.The mean%dHP in DCI was 29.23%and 10.66%in control.The mean%ΔCPPopt<−10 mmHg was 22.28%,and 5.90%in control.The%dHP(p<0.001)and the%ΔCPPopt<−10mmHg(p<0.001)was significantly longer in the DCI group.In multivariate logistic regression model,%ΔCPPopt<−10 mmHg(p<0.001)and%dHP(p<0.001)were independent risk factor for predicting DCI,and%ΔCPPopt<−10 mmHg(p=0.010)and%dHP(p=0.026)were independent risk factor for predicting unfavorable outcomes.Conclusions:The increase of duration of hypoperfusion events and duration of CPP below CPPopt over 10 mmHg,evaluated as time of lowered CPP,is highly indicative of DCI and unfavorable outcomes.
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 a Grant-in-Aid for Scientific Research from Mie Medical Research Foundation to Dr.Suzuki
文摘Neuroinflammation is a well-recognized consequence of subarachnoid hemorrhage（SAH）, and Toll-like receptor（TLR） 4 may be an important therapeutic target for post-SAH neuroinflammation. Of the TLR family members, TLR4 is expressed in various cell types in the central nervous system, and is unique in that it can signal through both the myeloid differentiation primary-response protein 88-dependent and the toll receptor associated activator of interferon-dependent cascades to coordinate the maximal inflammatory response. TLR4 can be activated by many endogenous ligands having damage-associated molecular patterns including heme and fibrinogen at the rupture of an intracranial aneurysm, and the resultant inflammatory reaction and thereby tissue damages may furthermore activate TLR4. It is widely accepted that the excreted products of TLR4 signaling alter neuronal functions. Previous studies have focused on the pathway through nuclear factor（NF）-κΒ signaling among TLR4 signaling pathways as to the development of early brain injury（EBI） such as neuronal apoptosis and blood-brain barrier disruption, and cerebral vasospasm. However, many findings suggest that both pathways via NF-κΒ and mitogen-activated protein kinases may be involved in EBI and cerebral vasospasm development. To overcome EBI and cerebral vasospasm is important to improve outcomes after SAH, because both EBI and vasopasm are responsible for delayed brain injuries or delayed cerebral ischemia, the most important preventable cause of poor outcomes after SAH. Increasing evidence has shown that TLR4 signaling plays an important role in SAH-induced brain injuries. Better understanding of the roles of TLR4 signaling in SAH will facilitate development of new treatments.
文摘In this manuscript a comprehensive coverage of recent developments in the drug therapy of vasospasm while providing the background information that neuroscientists need to understand its rationale. The range of new agents available for treatment of cerebral vasospasm is expanding rapidly along with rapid advances in pharmacology and physiology that are uncovering the mechanisms of this disease. Although there are many publications for treatment of cerebral vaso-spasm, most are focusing on different aspects of vasospasm treatment and many have limited value due to insufficient quality. Moreover, the complexity of this, in many cases deleterious condition, is enormous and the information needed to understand drug effects is accordingly often not readily available in a single source. A number of pharmacological and medical therapies are currently in use or being investigated in an attempt to reverse cerebral vasospasm, but only a few have proven to be useful. Current research efforts promise the eventual production of new medical therapies. At last, recommendations for the use of different treatment stages based on currently available clinical data are provided.
基金supported by a grant from the Forschungskommission der Medizinischen Fakultat,Albert-Ludwigs-Universitat Freiburg(SCHI1123/17,to MAS)。
文摘Infusion of the colloid hydroxyethylstarch has been used for volume substitution to maintain hemodynamics and microcirculation after e.g., severe blood loss.In the last decade it was revealed that hydroxyethylstarch can aggravate acute kidney injury, especially in septic patients.Because of the serious risk for critically ill patients, the administration of hydroxyethylstarch was restricted for clinical use.Animal studies and recently published in vitro experiments showed that hydroxyethylstarch might exert protective effects on the blood-brain barrier.Since the prevention of blood-brain barrier disruption was shown to go along with the reduction of brain damage after several kinds of insults, we revisit the topic hydroxyethylstarch and discuss a possible niche for the application of hydroxyethylstarch in acute brain injury treatment.
基金financially supported by grants from Key Research and Development Projects of Zhejiang Province (2020C03071)the Construction Fund of Medical Key Disciplines of Hangzhou (OO20200485, OO20200055)。
文摘BACKGROUND:A20 may be a neuroprotective factor.Herein,we aimed to investigate whether serum A20 levels were associated with disease severity,delayed cerebral ischemia(DCI),and outcome after aneurysmal subarachnoid hemorrhage(aSAH).METHODS:In this prospective cohort study containing 112 aSAH patients and 112 controls,serum A20 levels were quantified.At 90 d poststroke,Modified Rankin Scale(MRS) scores≥3 were defined as a poor outcome.All correlations and associations were assessed using multivariate analysis.RESULTS:Compared with controls,there was a significant elevation of serum A20 levels in patients(median 123.7 pg/mL vs.25.8 pg/mL;P<0.001).Serum A20 levels were independently correlated with Hunt-Hess scores(β 9.854;95% confidence interval [95% CI] 2.481-17.227,P=0.009) and modified Fisher scores(β 10.349,95% CI 1.273-19.424,P=0.026).Independent associations were found between serum A20 levels and poor outcome(odds ratio [OR] 1.015,95%CI 1.000-1.031,P=0.047) and DCI(OR 1.018,95% CI 1.001-1.035,P=0.042).Areas under the curve for predicting poor outcome and DCI were 0.771(95% CI 0.682-0.845) and 0.777(95% CI 0.688-0.850),respectively.Serum A20 levels ≥128.15 pg/mL predicted poor outcome,with a sensitivity of 73.9% and specificity of 74.2%,and A20 levels ≥160.55 pg/mL distinguished the risk of DCI with65.5% sensitivity and 89.2% specificity.Its ability to predict poor outcome and DCI was similar to those of Hunt-Hess scores and modified Fisher scores(both P>0.05).CONCLUSION:Enhanced serum A20 levels are significantly associated with stroke severity and poor clinical outcome after aSAH,implying that serum A20 may be a potential prognostic biomarker for aSAH.
