Stroke, Vol 23, 894-899, Copyright © 1992 by American Heart Association
D Xue, A Slivka and AM Buchan
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.
ARTICLES
Tirilazad reduces cortical infarction after transient but not permanent focal cerebral ischemia in rats
Department of Neurology and Neuroscience, Ottawa Civic Hospital, Ontario, Canada.
This article has been cited by other articles:
 |
|
 |
|
  E. Sena, P. Wheble, P. Sandercock, and M. Macleod Systematic Review and Meta-Analysis of the Efficacy of Tirilazad in Experimental Stroke Stroke, February 1, 2007; 38(2): 388 - 394. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Zausinger, K. Scholler, N. Plesnila, and R. Schmid-Elsaesser Combination Drug Therapy and Mild Hypothermia After Transient Focal Cerebral Ischemia in Rats Stroke, September 1, 2003; 34(9): 2246 - 2251. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. P. Derdeyn, J. D. Barr, A. Berenstein, John. J. Connors, J. E. Dion, G. R. Duckwiler, R. T. Higashida, C. M. Strother, T. A. Tomsick, and P. Turski The International Subarachnoid Aneurysm Trial (ISAT): A Position Statement from the Executive Committee of the American Society of Interventional and Therapeutic Neuroradiology and the American Society of Neuroradiology AJNR Am. J. Neuroradiol., August 1, 2003; 24(7): 1404 - 1408. [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Gilgun-Sherki, Z. Rosenbaum, E. Melamed, and D. Offen Antioxidant Therapy in Acute Central Nervous System Injury: Current State Pharmacol. Rev., June 1, 2002; 54(2): 271 - 284. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. J. Kavanagh and P. C. A. Kam Lazaroids: efficacy and mechanism of action of the 21-aminosteroids in neuroprotection Br. J. Anaesth., January 1, 2001; 86(1): 110 - 119. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Schmid-Elsaesser, E. Hungerhuber, S. Zausinger, A. Baethmann, H.-J. Reulen, and J. A. Zivin Combination Drug Therapy and Mild Hypothermia : A Promising Treatment Strategy for Reversible, Focal Cerebral Ischemia • Editorial Comment: A Promising Treatment Strategy for Reversible, Focal Cerebral Ischemia Stroke, September 1, 1999; 30 (9): e1891 - 1899. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Bittigau and C. Ikonomidou Topical Review: Glutamate in Neurologic Diseases J Child Neurol, November 1, 1997; 12(8): 471 - 485. [Abstract] [PDF]
|
|
|
|
|
|
R. Schmid-Elsaesser, S. Zausinger, E. Hungerhuber, N. Plesnila, A. Baethmann, and H.-J. Reulen Superior Neuroprotective Efficacy of a Novel Antioxidant (U-101033E) With Improved Blood-Brain Barrier Permeability in Focal Cerebral Ischemia Stroke, October 1, 1997; 28(10): 2018 - 2024. [Abstract] [Full Text]
|
|
|
|
 |
|
 E. D. Hall, P. K. Andrus, S. L. Smith, T. J. Fleck, H. M. Scherch, B. S. Lutzke, G. A. Sawada, J. S. Althaus, P. F. Vonvoigtlander, G. E. Padbury, et al. Pyrrolopyrimidines: Novel Brain-Penetrating Antioxidants with Neuroprotective Activity in Brain Injury and Ischemia Models J. Pharmacol. Exp. Ther., May 1, 1997; 281(2): 895 - 904. [Abstract] [Full Text]
|
|
|
|
|
|
R. F. Villa and A. Gorini Pharmacology of Lazaroids and Brain Energy Metabolism: A Review Pharmacol. Rev., March 1, 1997; 49(1): 99 - 136. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. B. Muller, O. Haraldseth, R. A. Jones, G. Sebastiani, C. F. Lindboe, G. Unsgard, and A. N. Oksendal Perfusion and Diffusion-Weighted MR Imaging for In Vivo Evaluation of Treatment With U74389G in a Rat Stroke Model Stroke, August 1, 1995; 26(8): 1453 - 1458. [Abstract] [Full Text]
|
|
|
|
 |
|
 M. D. Ginsberg Review : Neuroprotection in Brain Ischemia: An Update (Part II Neuroscientist, May 1, 1995; 1(3): 164 - 175. [Abstract] [PDF]
|
|
|
|
 |
|
 A. Olah, A. C. Cernaianu, T. Gaprindashvili, J. H. Cilley JR, M. M. Neuwirth, N. Ansari, and A. J. DelRossi Improvement of Spinal Cord Electrical Activity with Lazaroid (U74006F) During Operations on the Thoracic Aorta: Evaluation of a Novel Lipid Peroxidation Inhibitor Vascular and Endovascular Surgery, July 1, 1994; 28(6): 377 - 381. [Abstract] [PDF]
|
|