Tirilazad reduces cortical infarction after transient but not permanent focal cerebral ischemia in rats.
- 1 June 1992
- journal article
- abstracts
- Published by Ovid Technologies (Wolters Kluwer Health) in Stroke
- Vol. 23 (6), 894-899
- https://doi.org/10.1161/01.str.23.6.894
Abstract
We examined the cytoprotective effect of the lipid peroxidation inhibitor tirilazad mesylate (U74006F) in rodent models of neocortical infarction induced by transient and permanent focal cerebral ischemia. Wistar rats (experiment 1) and spontaneously hypertensive rats (experiment 2) were subjected to 2 hours of transient middle cerebral artery occlusion followed by 22 hours of reperfusion and pretreated with 10 mg/kg i.p. tirilazad, vehicle, or saline. Repeat doses were given at 4 and 10 hours after reperfusion. Spontaneously hypertensive rats were also subjected to permanent middle cerebral artery occlusion and either pretreated with tirilazad, vehicle, or saline intraperitoneally (experiment 3) or treated with either tirilazad or vehicle intravenously after ischemia (experiment 4). Cortical infarct volumes were measured 24 hours after the onset of either transient or permanent ischemia, and changes in core regional cerebral blood flow were monitored with laser Doppler flowmetry. Tirilazad reduced infarct volume after transient ischemia by 40% in Wistar rats (p = 0.08) (experiment 1) and 23% in spontaneously hypertensive rats (p less than 0.05) (experiment 2) but did not reduce infarction after permanent ischemia whether it was given intraperitoneally (experiment 3) or intravenously (experiment 4). Ischemic core blood flows were not affected during ischemia, nor were they affected during reperfusion after transient ischemia. Tirilazad reduces cortical infarction in transient but not permanent ischemia, an effect not related to improvement in regional cerebral blood flow. Tirilazad might prove to be useful as an adjuvant therapy after successful thrombolysis in acute stroke patients.This publication has 11 references indexed in Scilit:
- Failure of the Lipid Peroxidation Inhibitor, U74006F, to Prevent Postischemic Selective Neuronal InjuryJournal of Cerebral Blood Flow & Metabolism, 1992
- Effect of 21-aminosteroid U-74006F on lipid peroxidation in subarachnoid clotJournal of Neurosurgery, 1991
- Central nervous systems trauma and stroke: I. Biochemical considerations for oxygen radical formation and lipid peroxidationFree Radical Biology & Medicine, 1989
- The 21-aminosteroid inhibitors of lipid peroxidation: Reactions with lipid peroxyl and phenoxy radicalsFree Radical Biology & Medicine, 1989
- Continuous Measurement of Cerebral Cortical Blood Flow by Laser—Doppler Flowmetry in a Rat Stroke ModelJournal of Cerebral Blood Flow & Metabolism, 1989
- Clinical and instrumental evaluation of patients with ischemic stroke within the first six hoursJournal of the Neurological Sciences, 1989
- Focal Brain Ischemia in the Rat: Methods for Reproducible Neocortical Infarction Using Tandem Occlusion of the Distal Middle Cerebral and Ipsilateral Common Carotid ArteriesJournal of Cerebral Blood Flow & Metabolism, 1988
- Inhibition of arachidonic acid-induced vasogenic brain edema by the non-glucocorticoid 21-aminosteroid U74006FBrain Research, 1988
- Postischemic Cerebral Lipid Peroxidation In Vitro: Modification by Dietary Vitamin EJournal of Neurochemistry, 1985
- Lipid Peroxidation In Vivo Induced by Reversible Global Ischemia in Rat BrainJournal of Neurochemistry, 1984