COMPARATIVE PROTECTIVE EFFECTS OF VINCONATE, BACLOFEN, AND PENTOBARBITAL AGAINST NEURONAL DAMAGE FOLLOWING REPEATED BRIEF CEREBRAL-ISCHEMIA IN THE GERBIL BRAIN

We investigated the neuroprotective effects of vinconate (a vinca alkaloid derivative), baclofen (a GABA(B) receptor agonist), or pentobarbital (a GABA(A) receptor-effector) on neuronal damage following repeated brief cerebral ischemia in the gerbils. The animals were allowed to survive for 7 days after two or three 2-min ischemic insults induced by bilateral occlusion of the common carotid arteries. Morphological changes were evaluated in hippocampal CA1 sector and selectively vulnerable areas after two or three 2-min ischemic insults at 1-h intervals, respectively. Pretreatment with vinconate significantly reduced histopathological neuronal damage to the hippocampal CA1 sector following two 2-min ischemic insults. However, pretreatment with baclofen and pentobarbital failed to prevent neuronal damage. Pretreatment with vinconate also prevented neuronal damage to the frontal cortex, parietal cortex, and striatum following three 2-min ischemic insults. Nevertheless, this drug failed to prevent neuronal damage to the hippocampal CA1 sector and the thalamus. Results suggest that vinconate, a vica alkaloid derivative, can prevent neuronal damage after repeated brief cerebral ischemia, but not GABAergic agents, such as baclofen and pentobarbital. These findings are of interest in relation to the mechanisms of neuronal damage induced by repeated brief cerebral ischemia.