Neuroprotection and P450 2C11 upregulation after experimental transient ischemic attack
- PMID: 12053011
- DOI: 10.1161/01.str.0000016332.37292.59
Neuroprotection and P450 2C11 upregulation after experimental transient ischemic attack
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.
Similar articles
-
Animal models of transient ischemic attack: a review.Acta Neurol Belg. 2020 Apr;120(2):267-275. doi: 10.1007/s13760-020-01295-5. Epub 2020 Feb 11. Acta Neurol Belg. 2020. PMID: 32048230 Free PMC article. Review.
-
Reduced Severity of Outcome of Recurrent Ipsilateral Transient Cerebral Ischemia Compared with Contralateral Transient Cerebral Ischemia in Rats.J Stroke Cerebrovasc Dis. 2017 Dec;26(12):2915-2925. doi: 10.1016/j.jstrokecerebrovasdis.2017.07.035. Epub 2017 Sep 19. J Stroke Cerebrovasc Dis. 2017. PMID: 28893572
-
Hypoxic preconditioning and tolerance via hypoxia inducible factor (HIF) 1alpha-linked induction of P450 2C11 epoxygenase in astrocytes.J Cereb Blood Flow Metab. 2005 Aug;25(8):939-48. doi: 10.1038/sj.jcbfm.9600085. J Cereb Blood Flow Metab. 2005. PMID: 15729289
-
Functional hyperemia in the brain: hypothesis for astrocyte-derived vasodilator metabolites.Stroke. 1998 Jan;29(1):229-34. doi: 10.1161/01.str.29.1.229. Stroke. 1998. PMID: 9445355 Review.
-
Molecular characterization of an arachidonic acid epoxygenase in rat brain astrocytes.Stroke. 1996 May;27(5):971-9. doi: 10.1161/01.str.27.5.971. Stroke. 1996. PMID: 8623121
Cited by
-
Vascular contributions to cognitive impairment and dementia: the emerging role of 20-HETE.Clin Sci (Lond). 2021 Aug 13;135(15):1929-1944. doi: 10.1042/CS20201033. Clin Sci (Lond). 2021. PMID: 34374423 Free PMC article. Review.
-
Metabolism pathways of arachidonic acids: mechanisms and potential therapeutic targets.Signal Transduct Target Ther. 2021 Feb 26;6(1):94. doi: 10.1038/s41392-020-00443-w. Signal Transduct Target Ther. 2021. PMID: 33637672 Free PMC article. Review.
-
The interrelationship between cerebral ischemic stroke and glioma: a comprehensive study of recent reports.Signal Transduct Target Ther. 2019 Oct 12;4:42. doi: 10.1038/s41392-019-0075-4. eCollection 2019. Signal Transduct Target Ther. 2019. PMID: 31637020 Free PMC article. Review.
-
Is there a central role for the cerebral endothelium and the vasculature in the brain response to conditioning stimuli?Cond Med. 2018 Aug;1(5):220-232. Epub 2018 Aug 31. Cond Med. 2018. PMID: 30906928 Free PMC article.
-
Brain oxylipin concentrations following hypercapnia/ischemia: effects of brain dissection and dissection time.J Lipid Res. 2019 Mar;60(3):671-682. doi: 10.1194/jlr.D084228. Epub 2018 Nov 21. J Lipid Res. 2019. PMID: 30463986 Free PMC article.
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Medical