TIZANIDINE IS AN EFFECTIVE AGENT IN THE PREVENTION OF FOCAL CEREBRAL-ISCHEMIA IN RATS - AN EXPERIMENTAL-STUDY

BACKGROUND Focal cerebral ischemia secondary to cerebral vessel occlus ion is still an important cause of mortality and morbidity. Excitatory neurotransmitters are gathered in the extracellular space during isch emia and initiate or stimulate a series of pathophysiological biochemi cal processes and consequently lead to neuronal death. Tizanidine (San doz compound DS 103-282, 5-chloro-4,2 (2-imidazolin-2-yl-amino)-2,1,3- benzothiazol hydrochloride) is a selective alpha 2 adrenoreceptor agon ist which shows its effect by stimulating presynaptic alpha 2 adrenore ceptors in central ASPergic and GLUergic system by inhibiting aspartic acid and glutamic acid release. In this study, the effect of Tizanidi ne on reversible focal cerebral ischemia was evaluated. METHODS Cerebr al blood flow to the left hemisphere of adult Sprague-Dawley rats (n = 48) was temporarily interrupted by middle cerebral artery and bilater al common carotid artery occlusion for 3 hours in eight rats of each g roup. Tizanidine was given to each group of rats intraperitoneally bef ore the ischemic insult, 2 hours after ischemia, right after the reper fusion, 2 h after reperfusion, and 4 hours after reperfusion; the anim als survived for 24 hours after the reperfusion. After killing and tri phenyltetrasoliumchloride staining of brain slices, infarction volumes and ratios of the brains were calculated and the results were compare d with those of the control group. RESULTS Infarction volumes and infa rction 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 a fter 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 la ter. CONCLUSION This study shows that Tizanidine pretreatment before t he ischemic insult and the administration of the drug within the 2 hou rs after ischemia reduces ischemic damage significantly. Therefore, th is drug can be used as a protective and therapeutic agent in ischemic diseases. (C) 1998 by Elsevier Science Inc.