Viral reactivation from ganglia in subarachnoid hemorrhage

蛛网膜下腔出血中神经节的病毒再激活

• 批准号: 10242954
• 负责人: Melanie Walker
• 金额: $ 7.78万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-01 至 2023-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10242954
• 关键词: Acute; Admission activity; Adrenergic Agents; Anatomy; Aneurysmal Subarachnoid Hemorrhages; Antiviral Agents; Autonomic Pathways; Autonomic ganglion; Blood Flow Velocity; Blood Vessels; Brain; Caliber; Catecholamines; Cerebral Ischemia; Cerebrovascular Spasm; Cerebrovascular system; Cerebrum; Cessation of life; Clinical Management; Collection; Complication; Detection; Development; Digital Subtraction Angiography; Disease; Epinephrine; Eye; Future; Ganglia; Gland; Head and neck structure; Hemorrhage; Herpesviridae; Herpesvirus 1; Hospitalization; Incidence; Individual; Link; Literature; Measurement; Methods; Monitor; Morbidity - disease rate; Nerve; Nerve Fibers; Norepinephrine; Oral; Oral cavity; Pathway interactions; Patients; Perfusion; Peripheral; Prevention approach; Reporting; Research Personnel; Risk; Saliva; Sampling; Serum; Specimen; Subarachnoid Hemorrhage; Surface; Sympathetic Ganglia; Sympathetic Nervous System; Testing; Time; Vasospasm; Viral; Virus Shedding; Viscera; afferent nerve; autonomic nerve; functional outcomes; intracranial artery; mortality; novel strategies; predictive marker; prevent; reactivated HSV-1; response; risk stratification

Project Summary Aneurysmal subarachnoid hemorrhage (aSAH) is a devastating disease frequently leading to death or poor functional outcome. A major complication of aSAH is the development of cerebral vasospasm, which is defined as narrowing of the large and medium-sized intracranial arteries. Between 30-70% of patients develop vasospasm after aSAH and half of these may develop symptomatic delayed cerebral ischemia (DCI) with the incidence peaking in the second week after ictus. Despite improvements in the clinical management of aSAH over the last decade, DCI remains the single most important cause of morbidity and mortality in those patients who survive the initial hemorrhage. Limited information exists regarding underlying anatomic mechanisms of vasospasm in aSAH. Cerebral blood vessels on the surface of the brain are surrounded by nerve fibers that originate from sensory and autonomic nerve ganglia that are highly sensitive to sympathetic nervous system activity. Elevated levels of catecholamines have been well documented in aSAH, and in the acute setting, activation of perivascular sympathetic nerves leads to an increase in vascular tone and as a result, decreases brain perfusion. Paroxysmal cerebral vasospasm outside the acute setting suggests a different or delayed mechanism perhaps through the same anatomic pathway. We propose that herpesvirus reactivation in response to adrenergic activation of head and neck ganglia during aSAH will be directly related and thus temporally correlated with the occurrence of cerebral vasospasm. Given the shared anatomic pathways between glands, viscera and cerebral blood vessels, we propose that non-invasive, simultaneous monitoring of vascular tone and viral shedding from glandular secretions could demonstrate a correlation between viral reactivation and vasospasm after aSAH. If correct, antiviral agents would have the potential to reduce or prevent DCI in individuals with aSAH and analysis of oral and ocular secretions after acute aSAH may provide a simple and non-invasive predictive biomarker to assess risk of developing vasospasm.

项目概要 动脉瘤性蛛网膜下腔出血 (aSAH) 是一种破坏性疾病，经常导致 导致死亡或功能不良。 aSAH 的一个主要并发症是 脑血管痉挛，定义为大中型脑血管狭窄 颅内动脉。 30-70% 的患者在 aSAH 后出现血管痉挛，半数患者出现血管痉挛 这些人中的一些人可能会出现症状性迟发性脑缺血（DCI），其发病率 发作后第二周达到高峰。尽管临床管理有所改善 过去十年中，DCI 仍然是导致 aSAH 发病的最重要原因 以及那些在最初的出血中幸存下来的患者的死亡率。 关于血管痉挛的潜在解剖机制的信息有限 萨哈。大脑表面的脑血管被神经纤维包围 起源于对感觉和自主神经节高度敏感的 交感神经系统活动。儿茶酚胺水平升高 据记录，在 aSAH 中，以及在急性情况下，血管周围交感神经的激活 神经导致血管张力增加，从而减少大脑灌注。 急性环境之外的阵发性脑血管痉挛提示不同的或延迟的 机制可能通过相同的解剖途径。 我们提出，疱疹病毒重新激活是对头部和头部肾上腺素能激活的反应。 aSAH 期间的颈部神经节将直接相关，因此在时间上与 脑血管痉挛的发生。鉴于腺体之间共享的解剖通路， 内脏和脑血管，我们建议非侵入性、同步 监测血管张力和腺体分泌物的病毒脱落可以 证明 aSAH 后病毒再激活与血管痉挛之间存在相关性。如果正确的话， 抗病毒药物有可能减少或预防 aSAH 患者的 DCI 急性 aSAH 后口腔和眼部分泌物的分析可能提供简单且可靠的方法 用于评估发生血管痉挛风险的非侵入性预测生物标志物。