Neuroprotection and P450 2C11 upregulation after experimental transient ischemic attack

Nabil J. Alkayed, Toru Goyagi, Hung Dong Joh, Judith Klaus, David R. Harder, Richard J. Traystman, Patricia D. Hurn

Research output: Contribution to journalArticle

91 Scopus citations

Abstract

Background and Purpose - Transient ischemic attack (TIA) is a risk factor for stroke. However, TIA may also serve as a preconditioning stimulus, reducing damage from subsequent stroke. We tested the hypothesis that experimental TIA induces expression of P450 2C11, an arachidonic acid epoxygenase that produces vasodilator epoxyeicosatrienoic acids, leading to increased tissue perfusion and reduced stroke damage. Methods - Wistar rats underwent three 10-minute middle cerebral artery occlusions (TIA) or sham surgery. Three days later, animals were subjected to 2-hour middle cerebral artery occlusion and 24 hours of reperfusion. Brains were stained with 2,3,5-triphenyltetrazolium chloride for infarct size measurement or processed for quantification of P450 2C11 mRNA and protein with the use of RNase protection assay and Western blotting. Regional cerebral blood flow (CBF) at the end of 2-hour ischemia was measured in separate groups of rats with iodoantipyrine autoradiography. Results - Cerebral infarct was reduced by >50% in TIA- versus sham-preconditioned animals. 2C11 mRNA and protein were increased in ipsilateral hemisphere by 3 days after TIA but not sham surgery. Induction of 2C11 by TIA was also evident in ipsilateral hemisphere at 24 hours after 2-hour middle cerebral artery occlusion and 24 hours of reperfusion. End-ischemic regional CBF was not different between TIA- and sham-pretreated groups. Conclusions - We conclude that experimental TIA induces ischemic tolerance by a mechanism temporally linked to upregulation of P450 2C11. Enzyme induction does not attenuate ischemic severity by amplifying end-ischemic CBF.

Original languageEnglish (US)
Pages (from-to)1677-1684
Number of pages8
JournalStroke
Volume33
Issue number6
DOIs
StatePublished - 2002

Keywords

  • Cerebral ischemia, transient
  • Gene expression
  • Neuroprotection
  • Rats
  • Stroke, experimental

ASJC Scopus subject areas

  • Clinical Neurology
  • Cardiology and Cardiovascular Medicine
  • Advanced and Specialized Nursing

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    Alkayed, N. J., Goyagi, T., Joh, H. D., Klaus, J., Harder, D. R., Traystman, R. J., & Hurn, P. D. (2002). Neuroprotection and P450 2C11 upregulation after experimental transient ischemic attack. Stroke, 33(6), 1677-1684. https://doi.org/10.1161/01.STR.0000016332.37292.59