Selective sparing of NADPH-diaphorase neurons in neonatal hypoxia-ischemia.
Excitatory amino acids have been implicated in ischemic neuronal injury. To test this hypothesis in neonatal hypoxia-ischemia, lesions of the cortex and striatum were induced in 7-day-old rats by unilaterally ligating their carotid arteries and subjecting them to hypoxic conditions for 2 hours. Brains examined 1 week later demonstrated, within the regions of ischemic damage, a striking preservation of neurons that stained histochemically for nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d) activity. Concentrations of the neuropeptides somatostatin and neuropeptide Y, which colocalize in neurons containing NADPH-d, were unaffected in the areas of ischemic damage. The same pattern of injury with sparing of NADPH-d-reactive neurons was reproduced by focal microinfusion of the excitotoxin quinolinic acid, an endogenous N-methyl-d-aspartate (NMDA) agonist, into the striatum. These results support the hypothesis that neonatal hypoxic-ischemic injury is mediated through excitatory transmitters acting at the NMDA receptor and that the NADPH-d-reactive neurons in the neonate are resistant to excitotoxic damage. This pattern of cell vulnerability is unique to the developing striatum and may relate to the distinct pathological appearance of the basal ganglia that follows neonatal asphyxia.
Ferriero
D M
DM
Department of Neurology, University of California, San Francisco.
Arcavi
L J
LJ
Sagar
S M
SM
McIntosh
T K
TK
Simon
R P
RP
D000818:Animals; D000831:Animals, Newborn / Q000378:metabolism*; D001224:Aspartic Acid / Q000031:analogs & derivatives; D002545:Brain Ischemia / Q000201:enzymology / Q000378:metabolism / Q000473:pathology*; D002540:Cerebral Cortex / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D003342:Corpus Striatum / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D000860:Hypoxia / Q000201:enzymology / Q000378:metabolism / Q000473:pathology*; D016202:N-Methylaspartate; D009247:NADH, NADPH Oxidoreductases / Q000032:analysis; D009252:NADPH Dehydrogenase / Q000032:analysis; D009474:Neurons / Q000187:drug effects / Q000201:enzymology / Q000473:pathology*; D009478:Neuropeptide Y; D051381:Rats; D011919:Rats, Inbred Strains; D013004:Somatostatin
D009478:Neuropeptide Y; D001224:Aspartic Acid; D013004:Somatostatin; D016202:N-Methylaspartate; D009247:NADH, NADPH Oxidoreductases; D009252:NADPH Dehydrogenase