17β-estradiol attenuates breakdown of blood-brain barrier and hemorrhagic transformation induced by tissue plasminogen activator in cerebral ischemia

Mingchang Li, Zhan Zhang, Weiyun Sun, Raymond C. Koehler, Judy Huang

Research output: Contribution to journalArticle

Abstract

Tissue plasminogen activator (tPA) remains the only approved thrombolytic agent for the early treatment of ischemic stroke. However, treatment with tPA may lead to disruption of the blood-brain barrier and hemorrhagic transformation. 17β-estradiol (E2) has demonstrated efficacy in reduction of infarct volume in ischemic stroke models. The effects of acute administration of E2 on permeability of the blood-brain barrier and its ability to prevent hemorrhagic transformation in ischemic rats treated with tPA have not previously been studied. Here, we show that neurological deficits, brain water content, and Evan's blue extravasation were increased in ovariectomized female Wistar rats treated with tPA and attenuated in rats receiving E2. +. tPA. We also show that intracerebral hemoglobin and matrix metalloproteinase-9 activity were elevated with tPA treatment, and these increases were reduced by E2 treatment. Taken together, these data demonstrate that acute administration of E2 is capable of ameliorating some of the adverse effects of tPA administration, including the increase of matrix metalloproteinase-9 activity, blood-brain barrier permeability, and hemorrhagic transformation. These findings suggest a potential role for estrogen in thrombolytic treatment for ischemic stroke.

Original languageEnglish (US)
Pages (from-to)277-283
Number of pages7
JournalNeurobiology of Disease
Volume44
Issue number3
DOIs
StatePublished - Dec 1 2011

Keywords

  • Cerebral ischemia
  • Estrogen
  • Matrix metalloproteinase
  • Middle cerebral artery
  • Thrombolysis

ASJC Scopus subject areas

  • Neurology

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