GABA AND GLUTAMATE LEVELS IN THE SUBSTANTIA-NIGRA RETICULATA FOLLOWING REPETITIVE CEREBRAL-ISCHEMIA IN GERBILS

Repetitive cerebral ischemia produces more severe damage than a simila r single duration insult. We have previously shown that, in gerbils, d amage in the substantia nigra reticulata (SNr) is seen with repetitive insults rather than a single insult. We have also shown that there is a progressive decrease in the extracellular GABA in the striatum in t he days preceding such damage, speculating that a loss of GABA may be in part responsible for this damage. This study evaluates the GABA lev els in the SNr in animals exposed to repetitive ischemic insults. Each animal received a total of three ischemic insults of 3-min duration a t hourly intervals. In vivo microdialysis was carried out to analyze t he GABA and glutamate dialysate levels on Days 1, 3, 5, 7, and 14 foll owing the ischemic insult. In the control and treated (ischemic) anima ls, there was a significant increase in the GABA levels with the intro duction of nipecotic acid on Days 1, 3, 5, and 14. However, on Day 7 t here was a significant attenuation in the GABA response to nipecotic a cid in the treated animals in comparison to the controls. The glutamat e levels in the treated animals were similar to the control animals on Days 1, 3, 5, and 7. However, on Day 14 the glutamate levels were sig nificantly lower than on previous days. Our experiments for the first time measure extracellular glutamate and GABA responses in the SNr in animals exposed to repetitive ischemic insults. Our experiments show t hat there is a significant decrease in the GABA concentrations at a ti me when ischemic damage is developing in this region. This confirms ou r hypothesis that a decrease in GABA may be one factor contributing to neuronal damage during the period following repetitive ischemic insul ts. Further, the rebound increase in GABA levels on Day 14 with a conc omitant fall in glutamate levels would indicate that reparative proces ses are still active in the 2 weeks following the insult. (C) 1997 Aca demic Press.