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Selective sparing of NADPH‐diaphorase neurons in neonatal hypoxia‐ischemia
Author(s) -
Ferriero Donna M.,
Arcavi Lidia J.,
Sagar Stephen M.,
McIntosh Tracy K.,
Simon Roger P.
Publication year - 1988
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.410240512
Subject(s) - quinolinic acid , striatum , ischemia , nmda receptor , hypoxia (environmental) , neuropeptide y receptor , endocrinology , medicine , basal ganglia , neuropeptide , nadph dehydrogenase , biology , neuroscience , anesthesia , chemistry , receptor , central nervous system , biochemistry , nitric oxide synthase , dopamine , nitric oxide , amino acid , tryptophan , organic chemistry , oxygen
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 dinu‐cleotide 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.