Interleukin-6 mediates enhanced thrombus development in cerebral arterioles following a brief period of focal brain ischemia

Ya Hui Tang, Shantel Vital, Janice Russell, Hilary Seifert, D. Neil Granger

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

Objective: The cerebral microvasculature is rendered more vulnerable to thrombus formation following a brief (5.0. min) period of focal ischemia. This study examined the contribution of interleukin-6 (IL-6), a neuroprotective and prothrombotic cytokine produced by the brain, to transient ischemia-induced thrombosis in cerebral arterioles. Approach & results: The middle cerebral artery of C57BL/6J mice was occluded for 5min, followed by 24h of reperfusion (MCAo/R). Intravital fluorescence microscopy was used to monitor thrombus development in cerebral arterioles induced by light/dye photoactivation. Thrombosis was quantified as the time of onset of platelet aggregation on the vessel wall and the time for complete blood flow cessation. MCAo/R in wild type (WT) mice yielded an acceleration of thrombus formation that was accompanied by increased IL-6 levels in plasma and in post-ischemic brain tissue. The exaggerated thrombosis response to MCAo/R was blunted in WT mice receiving an IL-6 receptor-blocking antibody and in IL-6 deficient (IL-6-/-) mice. Bone marrow chimeras, produced by transplanting IL-6-/- marrow into WT recipients, did not exhibit protection against MCAo/R-induced thrombosis. Conclusions: The increased vulnerability of the cerebral vasculature to thrombus development after MCAo/R is mediated by IL-6, which is likely derived from brain cells rather than circulating blood cells. These findings suggest that anti-IL-6 therapy may reduce the likelihood of cerebral thrombus development after a transient ischemic attack.

Original languageEnglish (US)
Pages (from-to)351-357
Number of pages7
JournalExperimental Neurology
Volume271
DOIs
StatePublished - Sep 1 2015
Externally publishedYes

Keywords

  • Cerebral arterioles
  • Interleukin-6
  • Ischemia-reperfusion
  • Thrombosis
  • Transient ischemic attack

ASJC Scopus subject areas

  • Neurology
  • Developmental Neuroscience

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