CI-966, a GABA uptake inhibitor, antagonizes ischemia-induced neuronal degeneration in the gerbil.
1. Cerebral ischemia of 5 min duration was induced in unanesthetized gerbils by bilateral occlusion of the carotid arteries. 2. The extent of cerebral damage was assessed by the elevation of motor activity in comparison with pre-ischemic levels and by a histological assessment of the extent of neuronal degeneration of the CA1 area of the hippocampus. 3. The GABA transport inhibitor CI-966 (10 mg/kg i.p.) was tested for cerebroprotective activity in a gerbil stroke model. CI-966 reduced the extent of stroke injury as assessed by locomotor activity and measurement of hippocampal CA1 pyramidal cell injury. 4. It is proposed that enhancement of extracellular GABA levels during ischemia accounts for the cerebroprotective actions of CI-966.
Phillis
J W
JW
Department of Physiology, Wayne State University School of Medicine, Detroit, MI 48201, USA.
D000818:Animals; D001831:Body Temperature / Q000187:drug effects; D002545:Brain Ischemia / Q000473:pathology*; D018756:GABA Antagonists / Q000494:pharmacology*; D005849:Gerbillinae; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000473:pathology*; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D009410:Nerve Degeneration / Q000187:drug effects*; D017966:Pyramidal Cells / Q000187:drug effects*; D011725:Pyridines / Q000494:pharmacology*
D018756:GABA Antagonists; D011725:Pyridines; C067012:CI 966