D Xue1, A Slivka, A M Buchan. 1. Department of Neurology and Neuroscience, Ottawa Civic Hospital, Ontario, Canada.
Abstract
BACKGROUND AND PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
BACKGROUND AND PURPOSE: 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. METHODS:Wistar rats (experiment 1) and spontaneously hypertensiverats (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 hypertensiverats 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. RESULTS:Tirilazad reduced infarct volume after transient ischemia by 40% in Wistar rats (p = 0.08) (experiment 1) and 23% in spontaneously hypertensiverats (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. CONCLUSIONS: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 strokepatients.
Authors: Colin P Derdeyn; John D Barr; Alejandro Berenstein; John J Connors; Jacques E Dion; Gary R Duckwiler; Randall T Higashida; Charles M Strother; Thomas A Tomsick; Patrick Turski Journal: AJNR Am J Neuroradiol Date: 2003-08 Impact factor: 3.825
Authors: Ok-Nam Bae; Kelsey Serfozo; Seung-Hoon Baek; Ki Yong Lee; Anne Dorrance; Wilson Rumbeiha; Scott D Fitzgerald; Muhammad U Farooq; Bharath Naravelta; Archit Bhatt; Arshad Majid Journal: Stroke Date: 2012-12-18 Impact factor: 7.914