Local injection of kainic acid causes widespread degeneration of NADPH-d neurons and induction of NADPH-d in neurons, endothelial cells and reactive astrocytes.
Nitric oxide (NO), a diffusible gas, is a messenger molecule that mediates vascular dilatation and neural transmission. The enzyme nitric oxide synthase (NOS) present in neurons is activated by Ca2+ influx associated with activation of glutamate receptors. Cultured cortical neurons containing NOS are selectively vulnerable to injury by kainic acid (KA). However, the relationship between NOS neurons and excitotoxicity under in vivo conditions is not entirely clear. In the present study, we examined the time course and spatial distribution of changes in NOS neurons caused by an intracortical microinjection of KA in adult rats. NADPH-diaphorase (NADPH-d) histochemistry was used as a marker for NOS and the neuronal changes were correlated with changes in glial cells and endothelial cells. We demonstrated a rapid loss of NADPH-d neurons in the lesion center and degeneration of NADPH-d neurons and nerve terminals throughout ipsilateral cortex and hippocampus; the striatal neurons appeared to be unaffected. Subsequent to cortical neuronal degeneration, new NADPH-d activity appeared in proliferative reactive astrocytes and in endothelial cells at lesion periphery, and in neuronal groups at lesion periphery, in ipsilateral entorhinal cortex and bilateral hippocampus. These findings indicate that neurons expressing NADPH-d in cerebral cortex and hippocampus are selectively vulnerable to KA toxicity in vivo. The subsequent induction of NOS in neural and non-neural cells may be regarded as an adaptive response to the kainate-induced brain lesion.
Lei
D L
DL
Department of Neurobiology, Human Medical University, Changsha, People's Republic of China.
Yang
D L
DL
Liu
H M
HM
D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000201:enzymology*; D002540:Cerebral Cortex / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D002560:Cerebrovascular Circulation; D004730:Endothelium, Vascular / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology; D004790:Enzyme Induction; D006651:Histocytochemistry; D007267:Injections; D007608:Kainic Acid / Q000494:pharmacology*; D008297:Male; D009252:NADPH Dehydrogenase / Q000378:metabolism*; D009410:Nerve Degeneration; D009474:Neurons / Q000187:drug effects* / Q000201:enzymology*; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
D009252:NADPH Dehydrogenase; D007608:Kainic Acid