EFFECT OF NEONATAL HYPOXIA-ISCHEMIA ON NIGRO-STRIATAL DOPAMINE-RECEPTORS AND ON STRIATAL NEUROPEPTIDE-Y, DYNORPHIN-A AND SUBSTANCE-P CONCENTRATIONS IN RATS

Perinatal hypoxic-ischemic brain injury was induced in 7- to 8-day-old rats by ligating the left carotid artery with subsequent exposure to 9% oxygen atmosphere for 2.5 h. The animals were killed 7 days later a nd grouped according to the degree of brain injury sustained after hyp oxia-ischemia. Total protein content measured in striatum ipsilateral to the ligation, and dissected from brains showing extensive damage, w as reduced to 64% of contralateral tissue. The protein content was not altered in other groups including control animals exposed to air and in sham-operated animals exposed to hypoxic conditions. The concentrat ion of (pg/mg protein) and total (pg/striatum) striatal dynorphin A-li ke immunoreactivity (DLI) from brains with extensive damage were incre ased to 481% and 285% of the contralateral side, respectively. Hypoxia -ischemia increased striatal neuropeptide Y-like immunoreactivity (NPY LI) concentration from brains with extensive damage to 157% of contral ateral side, but when the results were expressed as total NPYLI conten t per striatum, NPYLI content in striatum with extensive damage remain ed unaltered. Substance P-like immunoreactivity (SPLI) concentration a nd total content per striatum from brains with extensive damage were r educed to 66% and 43% of the contralateral side, respectively. D-1 and D-2 receptor density in animals killed 10 days after injury was reduc ed by 24% and 22% of control, respectively, in striatum from brains wi th extensive damage. These results indicate complex changes in brain n europeptides following neonatal hypoxia-ischemia. Damage in the substa nce P system could have functional effects on dopaminergic transmissio n while the increase in NPYLI and in DLI concentrations may respective ly reflect the relative preservation from neuronal damage and possibly an increase in neuropeptide synthesis or decrease in release. The dec rease in SPLI concentration and the increase DLI concentration induced by hypoxia-ischemia suggests that these peptides may be present in se parate neurons.