Tizanidine is an effective agent in the prevention of focal cerebral ischemia in rats: An experimental study

Abstract

BACKGROUND Focal cerebral ischemia secondary to cerebral vessel occlusion is still an important cause of mortality and morbidity. Excitatory neurotransmitters are gathered in the extracellular space during ischemia and initiate or stimulate a series of pathophysiological biochemical processes and consequently lead to neuronal death. Tizanidine (Sandoz compound DS 103-282, 5-chloro-4,2 (2-imidazolin-2-yl-amino)-2,1,3-benzothiazol hydrochloride) is a selective alpha 2 adrenoreceptor agonist which shows its effect by stimulating presynaptic alpha 2 adrenoreceptors in central ASPergic and GLUergic system by inhibiting aspartic acid and glutamic acid release. In this study, the effect of Tizanidine on reversible focal cerebral ischemia was evaluated. METHODS Cerebral blood flow to the left hemisphere of adult Sprague-Dawley rats (n = 48) was temporarily interrupted by middle cerebral artery and bilateral common carotid artery occlusion for 3 hours in eight rats of each group. Tizanidine was given to each group of rats intraperitoneally before the ischemic insult, 2 hours after ischemia, right after the reperfusion, 2 h after reperfusion, and 4 hours after reperfusion; the animals survived for 24 hours after the reperfusion. After killing and triphenyltetrasoliumchloride staining of brain slices, infarction volumes and ratios of the brains were calculated and the results were compared with those of the control group. RESULTS Infarction volumes and infarction ratios of the Tizanidine group 1/2 hours before ischemia (143.7 +/- 6.34 mm(3) and 10.1 +/- 0.43%) and the Tizanidine group 2 hours after ischemia (145.6 +/- 6.32 mm(3) and 10.3 +/- 0.43%) were found to be significantly lower in favor of the Tizanidine groups when compared with those of the control group (173.9 +/- 6.38 mm(3) and 12,4 +/- 0.41%). Tizanidine is not effective if used just after reperfusion or later. CONCLUSION This study shows that Tizanidine pretreatment before the ischemic insult and the administration of the drug within the 2 hours after ischemia reduces ischemic damage significantly. Therefore, this drug can be used as a protective and therapeutic agent in ischemic diseases. (C) 1998 by Elsevier Science Inc.