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.
Stroke Branch, National Institutes of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892.
K
K
Kawai
L P
LP
Penix
N
N
Kawahara
C A
CA
Ruetzler
I
I
Klatzo
D000161:Acoustic Stimulation; D000818:Animals; D002545:Brain Ischemia / Q000209:etiology* / Q000378:metabolism; D004198:Disease Susceptibility; D005968:Glutamate Decarboxylase / Q000378:metabolism; D006323:Heart Arrest / Q000150:complications* / Q000378:metabolism; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012640:Seizures / Q000209:etiology* / Q000378:metabolism / Q000503:physiopathology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D005680:gamma-Aminobutyric Acid; D005968:Glutamate Decarboxylase