Human Cerebrospinal Fluid Macrophages and Outcome in Subarachnoid Hemorrhage

人脑脊液巨噬细胞和蛛网膜下腔出血的结果

• 批准号: 10372925
• 负责人: Khalid A. Hanafy
• 金额: $ 17.89万
• 依托单位: FLORIDA ATLANTIC UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-04-01 至 2023-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10372925
• 关键词: Admission activity; American; Aneurysmal Subarachnoid Hemorrhages; Apoptosis; Biological Assay; Biological Process; Blood Tests; Brain; Cell Line; Cells; Cerebral Ischemia; Cerebrospinal Fluid; Cerebrum; Cessation of life; Clinical; Clinical Trials; Cognitive; Data; Detection; Disease; Erythrocytes; Flow Cytometry; Focal Neurologic Deficits; Functional disorder; Future; Hematoma; Heme; Hour; Human; Immune; Immunohistochemistry; Impaired cognition; Individual; Infarction; Inflammation; Inflammatory; Inflammatory Response; Injury; Magnetic Resonance Imaging; Measures; Microglia; Monitor; Morbidity - disease rate; Mus; Neurologic; Neuronal Injury; Neurons; Organ; Outcome; Pathology; Patients; Phagocytosis; Play; Publishing; Research; Resolution; Risk Factors; Role; Subarachnoid Hemorrhage; Time; Tissues; Translations; Triage; Vasospasm; X-Ray Computed Tomography; base; bench to bedside; clinical examination; cytokine; disability; heme a; high risk; individual patient; macrophage; mortality; mouse model; neuron apoptosis; new therapeutic target; novel; personalized approach; prevent; prospective; targeted treatment; virtual

The focus of research in aneurysmal subarachnoid hemorrhage for the last 30 years has been on understanding the pathophysiology of vasospasm and attempts to ameliorate it. Unfortunately, even when vasospasm is effectively treated, there is no improvement in death or disability. Subsequently, a novel concept and more effective endpoint for clinical trials emerged over the last 10 years: delayed cerebral ischemia (DCI), referring to new infarctions causing focal neurological deficits. Studies have shown that the occurrence of DCI is independently associated with morbidity, at least. The causes of DCI remains uncertain, but we believe that a focus on the cerebral inflammatory response (CIR) to the persistent heme burden that remains is a likely culprit for the initiation of DCI. While many independent associations for DCI exist, none account for the CIR in any way. Perhaps a focus on expedited hematoma resolution as well as finding some measure of the CIR to increase accuracy of DCI prediction is in order. Based on our mouse model of SAH, we found that the tissue resident macrophages of the brain are responsible for the majority of the CIR as well as for hematoma resolution. In our proposal, we use each individual patient’s cerebrospinal fluid (CSF) macrophages that are of tissue resident origin to study DCI and hematoma resolution. Specifically, we put these special macrophages in contact with a human neuronal cell line as a way to predict whether or not a patient might have DCI. We use flow cytometry to determine if the macrophages in the CSF are phagocytosing significant amounts of red blood cells to determine if the hematoma will resolve faster, and if this results in less DCI. We believe that these studies could provide a personalized approach to predicting DCI and hematoma resolution based on an individual’s innate immune profile. If validated in a prospective trial, these cell-based assays could be used to empirically discover new therapeutic targets for agents that could enhance RBC phagocytosis and reduce neuronal apoptosis by CSF macrophages, in an example of “bedside to bench” reverse translation.

近30年来，动脉瘤性蛛网膜下腔出血的研究重点是

项目成果

Microglial TLR4 is Critical for Neuronal Injury and Cognitive Dysfunction in Subarachnoid Hemorrhage.

• DOI: 10.1007/s12028-022-01552-w
• 发表时间: 2022-12
• 期刊: Neurocritical care
• 影响因子: 3.5

Quantitative susceptibility mapping improves cerebral microbleed detection relative to susceptibility-weighted images.

相对于磁敏度加权图像，定量磁敏图可改善脑微出血检测。

• DOI: 10.1111/jon.13054
• 发表时间: 2023
• 期刊: Journal of neuroimaging : official journal of the American Society of Neuroimaging
• 作者: Lee,Kyuwon;Ellison,Brian;Selim,Magdy;Long,NgoH;Filippidis,Aristotelis;Thomas,AjithJ;Spincemaille,Pascal;Wang,Yi;Soman,Salil
• 通讯作者: Soman,Salil

Brain FADE syndrome: the final common pathway of chronic inflammation in neurological disease.

• DOI: 10.3389/fimmu.2024.1332776
• 发表时间: 2024
• 期刊: Frontiers in immunology
• 影响因子: 7.3

Gender differences in Alzheimer's may be associated with TLR4-LYN expression in damage associated microglia and neuronal phagocytosis.

• DOI: 10.1002/jcp.30916
• 发表时间: 2022-11
• 期刊: Journal of Cellular Physiology
• 影响因子: 5.6
• 作者: R. Islam;Robin Rajan;Hadi Choudhary;F. Vrionis;Khalid A. Hanafy