Neuroprotection and P450 2C11 upregulation after experimental transient ischemic attack. Stroke 2002 Jun;33(6):1677-84
Date
06/08/2002Pubmed ID
12053011DOI
10.1161/01.str.0000016332.37292.59Scopus ID
2-s2.0-0036277938 (requires institutional sign-in at Scopus site) 97 CitationsAbstract
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.
Author List
Alkayed NJ, Goyagi T, Joh HD, Klaus J, Harder DR, Traystman RJ, Hurn PDMESH terms used to index this publication - Major topics in bold
AnimalsAryl Hydrocarbon Hydroxylases
Autoradiography
Blood Flow Velocity
Blotting, Western
Brain
Cerebrovascular Circulation
Cytochrome P-450 Enzyme System
Disease Models, Animal
Enzyme Induction
Female
Infarction, Middle Cerebral Artery
Ischemic Attack, Transient
Ischemic Preconditioning
Liver
Male
RNA, Messenger
Rats
Rats, Wistar
Reperfusion
Steroid 16-alpha-Hydroxylase
Steroid Hydroxylases
Up-Regulation
