Attenuated Neurotransmitter Release and Spreading Depression-Like Depolarizations after Focal Ischemia in Mutant Mice with Disrupted Type I Nitric Oxide Synthase Gene

摘要: Nitric oxide (NO) plays a complex role in the pathophysiology of cerebral ischemia. In this study, mutant mice with disrupted type I (neuronal) NO synthase (nNOS) were compared wild-type littermates after permanent focal Cerebral blood flow central and peripheral zones ischemic distribution measured laser doppler flowmetry. Simultaneously, microdialysis electrodes used to measure extracellular amino acid concentrations DC potential these same locations. Blood was reduced <25 60% baseline levels zones, respectively; there no differences nNOS mutants versus mice. Within zone, potentials rapidly shifted -20 mV all periphery, spreading depression (SD)-like waves depolarization observed. SD-like events significantly fewer Concurrent hemodynamic electrophysiological perturbations, elevations acids occurred There detectable between periphery. However, zone ischemia, glutamate GABA lower mutants. Twenty-four hour infarct volumes smaller than their littermates. Overall, number depolarizations integrated efflux correlated size. These results suggest that derived from isoform contributes tissue damage ischemia by amplifying excitotoxic release core deleterious