Soluble vascular endothelial-cadherin in CSF after subarachnoid hemorrhage

Hajime Takase, Sherry Hsiang Yi Chou, Gen Hamanaka, Ryo Ohtomo, Mohammad R. Islam, Jong Woo Lee, Liangge Hsu, Justin Mathew, Estefania Reyes-Bricio, Kazuhide Hayakawa, Changhong Xing, Ming Ming Ning, Xiaoying Wang, Ken Arai, Eng H. Lo, Josephine Lok, Josephine Lok

Research output: Contribution to journalArticlepeer-review

14 Scopus citations


ObjectiveTo determine if CSF and plasma levels of soluble vascular endothelial (sVE)-cadherin are associated with functional outcome after subarachnoid hemorrhage (SAH) and to investigate sVE-cadherin effects on microglia.MethodsSerial CSF and plasma were collected from prospectively enrolled patients with nontraumatic SAH from a ruptured aneurysm in the anterior circulation and who required an external ventricular drain for clinical indications. Patients with normal-pressure hydrocephalus without SAH served as controls. For prospective assessment of long-Term outcomes at 3 and 6 months after SAH, modified Rankin Scale scores (mRS) were obtained and dichotomized into good (mRS ≤ 2) vs poor (mRS > 2) outcome groups. For SAH severity, Hunt and Hess grade was assessed. Association of CSF sVE-cadherin levels with long-Term outcomes, HH grade, and CSF tumor necrosis factor (TNF)-α levels were evaluated. sVE-cadherin effects on microglia were also studied.ResultssVE-cadherin levels in CSF, but not in plasma, were higher in patients with SAH and were associated with higher clinical severity and higher CSF TNF-α levels. Patients with SAH with higher CSF sVE-cadherin levels over time were more likely to develop worse functional outcome at 3 months after SAH. Incubation of cultured microglia with sVE-cadherin resulted in increased inducible nitric oxide synthase, interleukin-1β, reactive oxygen species, cell soma size, and metabolic activity, consistent with microglia activation. Microinjection of sVE-cadherin fragments into mouse brain results in an increased number of microglia surrounding the injection site, compared to injection of denatured vascular endothelial-cadherin fragments.ConclusionsThese results support the existence of a novel pathway by which sVE-cadherin, released from injured endothelium after SAH, can shift microglia into a more proinflammatory phenotype and contribute to neuroinflammation and poor outcome in SAH.

Original languageEnglish (US)
Pages (from-to)e1281-e1293
Issue number12
StatePublished - Mar 24 2020

ASJC Scopus subject areas

  • Clinical Neurology


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