THE NEUROPROTECTIVE EFFECTS OF GAMMA-VINYL GABA IN TRANSIENT GLOBAL-ISCHEMIA - A MORPHOLOGICAL-STUDY WITH EARLY AND DELAYED EVALUATIONS

Enhancing inhibitory mechanisms has been shown to improve neuronal sur vival after transient focal or global ischemia. In most studies, histo logical evaluations have been confined to the CA1 region of the hippoc ampus up to 7 days after an ischemic insult. We have previously shown that continuous intra-ventricular infusion of gamma-vinyl GABA (GVG) r esults in significant protection after cerebral ischemia. This present study was designed to assess histological and behavioral function at 7 and 28 days after a single 5 min ischemic episode in gerbils. One se t of animals received the medication 30 min before the insult and the other set at 1 h after the insult. Evaluation at 7 days showed signifi cant protection in most regions of the brain in both the pre- and post -ischemic treated animals in comparison to the controls. Delayed evalu ation at 28 days showed significant protection only in the pre-ischemi c treated animals. Behavioral testing with Morris water maze showed no differences in either pre- or post-ischemic treated animals when comp ared to saline-treated ischemic controls. Our study clearly demonstrat es the usefulness of delayed evaluation in the assessment of 'true' ne uronal protection. Pre-ischemic treated animals showed persistent and true neuronal protection, in contrast to a temporary protection as see n at 7 days in the post-ischemic treated animals. The lack of behavior al improvement in the pre- and post-ischemic treated animals suggests that morphological protection alone cannot be considered as the sole c riterion for successful outcome.