Intracerebral hemorrhage(ICH)causes hematoma formation,leading to PHE,which is associated with leukocyte mobilization and increased inflammation at the site of brain injury.However,the fate of accumulated leukocytes w...Intracerebral hemorrhage(ICH)causes hematoma formation,leading to PHE,which is associated with leukocyte mobilization and increased inflammation at the site of brain injury.However,the fate of accumulated leukocytes within the hematoma and their impact on PHE expansion remain unknown.We performed single-cell immune profiling of hematoma cells from patients with acute ICH and reported a distinct phenotypic transformation of CD8^(+)T cells within the hematoma during the first 24 h after onset.In addition to enhanced IFN-γproduction and migration capacity,these CD8^(+)T cells displayed remarkable glycolytic signatures.The metabolic fitness and functional reprogramming of hematomal CD8^(+)T cells are associated with the transcription factor FOXO1.Single-cell profiling of brain-infiltrating CD8^(+)T cells within the perihematomal tissues of ICH patients and cell culture assays revealed their capacity to activate microglia via the production of IFN-γ.Furthermore,the removal of hematomal CD8^(+)T cells reduced neuroinflammation,PHE expansion and neurological deficits in ICH mice.Thus,CD8^(+)T cells undergo metabolic and functional reprogramming within the hematoma during the acute phase of ICH,which contributes to PHE formation and neurological deterioration.展开更多
BACKGROUND Hematoma expansion(HE)typically portends a poor prognosis in spontaneous intracerebral hemorrhage(ICH).Several radiographic and laboratory values have been proposed as predictive markers of HE.AIM To perfor...BACKGROUND Hematoma expansion(HE)typically portends a poor prognosis in spontaneous intracerebral hemorrhage(ICH).Several radiographic and laboratory values have been proposed as predictive markers of HE.AIM To perform a systematic review and meta-analysis on the association of neu-trophil-to-lymphocyte ratio(NLR)and HE in ICH.A secondary outcome exa-mined was the association of NLR and perihematomal(PHE)growth.METHODS Three databases were searched(PubMed,EMBASE,and Cochrane)for studies evaluating the effect of NLR on HE and PHE growth.The inverse variance me-thod was applied to estimate an overall effect for each specific outcome by combining weighted averages of the individual studies’estimates of the logarithm odds ratio(OR).Given heterogeneity of the studies,a random effect was applied.Risk of bias was analyzed using the Newcastle-Ottawa Scale.The study was conducted following the Preferred Reporting Items for Systematic Review and Meta-analysis guidelines.The protocol was registered in PROSPERO(No.CRD42024549924).RESULTS Eleven retrospective cohort studies involving 2953 patients were included in the meta-analysis.Among those,HE was investigated in eight studies,whereas PHE growth was evaluated in three.Blood sample was obtained on admission in ten studies,and at 24 hours in one study.There was no consensus on cut-off value among the studies.NLR was found to be significantly associated with higher odds of HE(OR=1.09,95%CI:1.04-1.15,I2=86%,P<0.01),and PHE growth(OR=1.28,95%CI:1.19-1.38,I2=0%,P<0.01).Qualitative analysis of each outcome revealed overall moderate risk of bias mainly due to lack of control for systemic confounders.CONCLUSION The available literature suggests that a possible association may exist between NLR on admission and HE,and PHE growth.Future studies controlled for systemic confounders should be designed to consolidate this finding.If confirmed,NLR could be added as a readily available and inexpensive biomarker to identify a subgroup of patients at higher risk of developing HE.展开更多
Intracerebral hemorrhage(ICH) remains the second-most common form of stroke with high morbidity and mortality.ICH can be divided into two pathophysiological stages:an acute primary phase,including hematoma volume expa...Intracerebral hemorrhage(ICH) remains the second-most common form of stroke with high morbidity and mortality.ICH can be divided into two pathophysiological stages:an acute primary phase,including hematoma volume expansion,and a subacute secondary phase consisting of blood-brain barrier disruption and perihematomal edema expansion.To date,all major trials for ICH have targeted the primary phase with therapies designed to reduce hematoma expansion through blood pressure control,surgical evacuation,and hemostasis.However,none of these trials has resulted in improved clinical outcomes.Magnesium is a ubiquitous element that also plays roles in vasodilation,hemostasis,and blood-brain barrier preservation.Animal models have highlighted potential therapeutic roles for magnesium in neurological diseases specifically targeting these pathophysiological mechanisms.Retrospective studies have also demonstrated inverse associations between admission magnesium levels and hematoma volume,hematoma expansion,and clinical outcome in patients with ICH.These associations,coupled with the multifactorial role of magnesium that targets both primary and secondary phases of ICH,suggest that magnesium may be a viable target of study in future ICH studies.展开更多
基金supported in part by the National Science Foundation of China(U21A20360,82371349,82225015,82171284,82200279 and 82101373)the National Key Research and Development Project of China(2021ZD0202400)+2 种基金the National Science and Technology Major Project of China(2024ZD0527905)the New Cornerstone Science Foundation through the XPLORER PRIZE,the Science and Technology Development Fund of Tianjin Education Commission for Higher Education Grants(2021ZD035)the Major Scientific Research Program for Young and Middle-aged Health Professionals of Fujian Province(2022ZQNZD005).
文摘Intracerebral hemorrhage(ICH)causes hematoma formation,leading to PHE,which is associated with leukocyte mobilization and increased inflammation at the site of brain injury.However,the fate of accumulated leukocytes within the hematoma and their impact on PHE expansion remain unknown.We performed single-cell immune profiling of hematoma cells from patients with acute ICH and reported a distinct phenotypic transformation of CD8^(+)T cells within the hematoma during the first 24 h after onset.In addition to enhanced IFN-γproduction and migration capacity,these CD8^(+)T cells displayed remarkable glycolytic signatures.The metabolic fitness and functional reprogramming of hematomal CD8^(+)T cells are associated with the transcription factor FOXO1.Single-cell profiling of brain-infiltrating CD8^(+)T cells within the perihematomal tissues of ICH patients and cell culture assays revealed their capacity to activate microglia via the production of IFN-γ.Furthermore,the removal of hematomal CD8^(+)T cells reduced neuroinflammation,PHE expansion and neurological deficits in ICH mice.Thus,CD8^(+)T cells undergo metabolic and functional reprogramming within the hematoma during the acute phase of ICH,which contributes to PHE formation and neurological deterioration.
文摘BACKGROUND Hematoma expansion(HE)typically portends a poor prognosis in spontaneous intracerebral hemorrhage(ICH).Several radiographic and laboratory values have been proposed as predictive markers of HE.AIM To perform a systematic review and meta-analysis on the association of neu-trophil-to-lymphocyte ratio(NLR)and HE in ICH.A secondary outcome exa-mined was the association of NLR and perihematomal(PHE)growth.METHODS Three databases were searched(PubMed,EMBASE,and Cochrane)for studies evaluating the effect of NLR on HE and PHE growth.The inverse variance me-thod was applied to estimate an overall effect for each specific outcome by combining weighted averages of the individual studies’estimates of the logarithm odds ratio(OR).Given heterogeneity of the studies,a random effect was applied.Risk of bias was analyzed using the Newcastle-Ottawa Scale.The study was conducted following the Preferred Reporting Items for Systematic Review and Meta-analysis guidelines.The protocol was registered in PROSPERO(No.CRD42024549924).RESULTS Eleven retrospective cohort studies involving 2953 patients were included in the meta-analysis.Among those,HE was investigated in eight studies,whereas PHE growth was evaluated in three.Blood sample was obtained on admission in ten studies,and at 24 hours in one study.There was no consensus on cut-off value among the studies.NLR was found to be significantly associated with higher odds of HE(OR=1.09,95%CI:1.04-1.15,I2=86%,P<0.01),and PHE growth(OR=1.28,95%CI:1.19-1.38,I2=0%,P<0.01).Qualitative analysis of each outcome revealed overall moderate risk of bias mainly due to lack of control for systemic confounders.CONCLUSION The available literature suggests that a possible association may exist between NLR on admission and HE,and PHE growth.Future studies controlled for systemic confounders should be designed to consolidate this finding.If confirmed,NLR could be added as a readily available and inexpensive biomarker to identify a subgroup of patients at higher risk of developing HE.
文摘Intracerebral hemorrhage(ICH) remains the second-most common form of stroke with high morbidity and mortality.ICH can be divided into two pathophysiological stages:an acute primary phase,including hematoma volume expansion,and a subacute secondary phase consisting of blood-brain barrier disruption and perihematomal edema expansion.To date,all major trials for ICH have targeted the primary phase with therapies designed to reduce hematoma expansion through blood pressure control,surgical evacuation,and hemostasis.However,none of these trials has resulted in improved clinical outcomes.Magnesium is a ubiquitous element that also plays roles in vasodilation,hemostasis,and blood-brain barrier preservation.Animal models have highlighted potential therapeutic roles for magnesium in neurological diseases specifically targeting these pathophysiological mechanisms.Retrospective studies have also demonstrated inverse associations between admission magnesium levels and hematoma volume,hematoma expansion,and clinical outcome in patients with ICH.These associations,coupled with the multifactorial role of magnesium that targets both primary and secondary phases of ICH,suggest that magnesium may be a viable target of study in future ICH studies.
