Spatial and temporal alterations in the GABA shunt in the gerbil hippocampus following transient ischemia

In the present study, we have identified the alteration in the expressions of GABA shunt-associated enzymes and the GABA transporter in order to determine the relationship between the neuronal damage and GABA metabolism following ischemia. At 30 min post-ischemia, the immunoreactivities of the glutamic acid decarboxylase (GAD) isoforms were markedly elevated in the CA1 region, as compared with the sham operated group. At 3-12 h post-ischemia, their immunoreactivities recovered at the sham level. These patterns were similarly observed up to 12 h following ischemia insult. However, the intensity of GAD67 was markedly increased at 24 h post-ischemic insult. The temporal changes in GABA transporter 1 (GAT-1) expressions were similar to that of GAD67, but not GAD65, expression, at least prior to 12 h after ischemic insults. GAT-1 immunoreactivity was significantly elevated in the CA1 region posterior to 12 h post-ischemia. Both succinic semialdehyde dehydrogenase (SSADH) and succinic semialdehyde reductase (SSAR) immunoreactivities were not altered in GABAergic neurons following ischemia. In contrast, in pyramidal cells, both SSADH and SSAR immunoreactivities showed chronological alterations in the CA1 region. Thus, our findings suggest that the differential alterations of GABA metabolism may be one of the important factors in neuronal damages induced by ischemia.