fg-9041 and Atrophy

We studied the development of brain atrophy after transient focal ischemia in rats. The animals were subjected to cerebral ischemia induced by embolization of the right middle cerebral artery (MCA) for 60 min. The brains were studied morphologically 7 days, 1 month, 3 months and 9 months after recirculation. In addition, the effects of a new calcium antagonist, KB-2796, and a glutamate receptor antagonist, 6,7-dinitroquinoxaline-2,3-dione (DNQX); were evaluated in this model 1 month after ischemia. The hemispheric volume of the ipsilateral ischemic side, expressed as a percentage of that on the contralateral non-ischemic side, was 99% in the sham operation group, 94% at 7 days, 87% at 1 month, 68% at 3 months and 65% at 9 months. Atrophy of the striatum and cortex, but not the hippocampus, was observed 1 month after ischemia. Atrophy of the ipsilateral substantia nigra and the thalamus, which are remote from the ischemic region, was observed 7 days and 1 month, respectively, after ischemia. Correlations between the extent of the atrophy in the striatum and that in the substantia nigra and between the extent of the atrophy in the cortex and in the thalamus were statistically significant. Treatment with KB-2796 or DNQX administered intraperitoneally at a dose of 10 mg/kg twice 30 min before ischemia and immediately after ischemia was effective in reducing the extent of atrophy in both the ipsilateral ischemic and non-ischemic regions. These results suggest that brain atrophy on the ipsilateral ischemic side develops time-sequentially after transient focal ischemia and that ischemia affects not only the primary ischemic focus but also remote regions through transsynaptic connections, and that KB-2796 and DNQX have beneficial effects on atrophy in the chronic phase after ischemia.

Topics: Animals; Atrophy; Brain; Calcium Channel Blockers; Cerebral Arteries; Excitatory Amino Acid Antagonists; Ischemic Attack, Transient; Male; Piperazines; Quinoxalines; Rats; Rats, Wistar; Time Factors