Development of susceptibility to audiogenic seizures following cardiac arrest cerebral ischemia in rats.

Susceptibility to audiogenic seizures (AGS) was investigated in Sprague-Dawley rats subjected to cardiac arrest cerebral ischemia (CACI), produced by compression of the major cardiac vessels. The onset of AGS was regularly observed 1 day after CACI of > 5 min duration. The duration of postischemic susceptibility to AGS was directly related to the density of cerebral ischemia, with 50% of more severely ischemic animals still showing AGS susceptibility 8 weeks after CACI. Lesioning of the inferior colliculi (IC) abolished the onset of AGS; no such effect was observed after lesioning the medial geniculate (MG). Glutamic acid decarboxylase (GAD) immunochemistry revealed approximately 50% loss of GAD-positive neurons in the IC, which was similar in animals with various durations of AGS susceptibility. Otherwise, there was a conspicuous sprouting of gamma-aminobutyric acid (GABA)-ergic terminals in the ventral thalamic nuclei, which peaked approximately 1 month after the CACI. Evaluation of GABA-A inhibitory function in the hippocampus by the paired pulse stimulation revealed changes indicating loss of GABA-A inhibition coinciding with the onset of AGS, and its return in animals tested 2 months after CACI. Our observations suggest a potential role of GABA-ergic dysfunction in the postischemic development of AGS.