Short-term cerebral ischemia causes the dysfunction of interneurons and more excitation of pyramidal neurons in rats.
Neural excitotoxicity is a typical factor in the early phase pathogenesis of cerebral ischemia. Its cellular and molecular mechanisms are still unclear and clinical approaches are still lacking of promising therapies. We have examined the vulnerability of cortical neurons to short-term ischemia in rats by simultaneously analyzing the activities of inhibitory and principal neurons in brain slices. Our results demonstrate that short-term in vitro ischemia permanently impairs the excitability of inhibitory neurons (IN) and synaptic transmission mediated by gamma-aminobutyric acid (GABA). However, principal neurons appear to be more exciting during the reperfusion. The vulnerability of inhibitory neurons to ischemia acquires during postnatal development. Our findings signify a major contribution of the ischemic dysfunction of inhibitory neurons to neural excitotoxicity as well as a strategy to prevent the progress of ischemic stroke by protecting inhibitory neurons.
Wang
Jin Hui
JH
Department of Molecular Biosciences, University of Kansas, Lawrence, KS 66045, USA. jinhwang@ku.edu
D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D000831:Animals, Newborn; D001640:Bicuculline / Q000494:pharmacology; D002545:Brain Ischemia / Q000503:physiopathology*; D002540:Cerebral Cortex / Q000503:physiopathology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology; D066298:In Vitro Techniques; D007395:Interneurons / Q000502:physiology*; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology; D018408:Patch-Clamp Techniques / Q000379:methods; D017966:Pyramidal Cells / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D018691:Excitatory Amino Acid Antagonists; D018756:GABA Antagonists; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D015763:2-Amino-5-phosphonovalerate; D001640:Bicuculline