Viral reactivation from ganglia in subarachnoid hemorrhage

项目摘要 动脉瘤性蛛网膜下腔出血（aSAH）是一种毁灭性的疾病， 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后发生血管痉挛， 这些可能发展为症状性迟发性脑缺血（DCI）， 发病后第二周达到高峰尽管临床管理有所改善， 在过去的十年中，DCI仍然是aSAH发病的最重要原因 和死亡率之间的关系。 关于血管痉挛的潜在解剖机制的信息有限， 啊。大脑表面的脑血管被神经纤维包围着 它们来源于感觉和自主神经节， 交感神经系统活动高水平的儿茶酚胺 在aSAH中记录，在急性环境中，血管周围交感神经激活 神经损伤导致血管紧张度增加，从而减少脑灌注。 急性期以外的阵发性脑血管痉挛提示不同的或延迟的 可能通过相同的解剖学途径。 我们认为，疱疹病毒的再激活是对肾上腺素能激活头部和 aSAH期间的颈神经节将直接相关，因此在时间上与 发生脑血管痉挛。考虑到腺体之间共有的解剖学通路， 内脏和脑血管，我们建议，非侵入性，同时 监测血管张力和腺分泌物中的病毒脱落， 证明了aSAH后病毒再活化和血管痉挛之间的相关性。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以提供一个简单的， 评估发生血管痉挛风险的非侵入性预测生物标志物。

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.