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 and grouped according to the degree of brain injury sustained after hypoxia-ischemia. Total protein content measured in striatum ipsilateral to the ligation, and dissected from brains showing extensive damage, was 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 concentration of (pg/mg protein) and total (pg/striatum) striatal dynorphin A-like immunoreactivity (DLI) from brains with extensive damage were increased to 481% and 285% of the contralateral side, respectively. Hypoxia-ischemia increased striatal neuropeptide Y-like immunoreactivity (NPYLI) concentration from brains with extensive damage to 157% of contralateral side, but when the results were expressed as total NPYLI content per striatum, NPYLI content in striatum with extensive damage remained unaltered. Substance P-like immunoreactivity (SPLI) concentration and total content per striatum from brains with extensive damage were reduced to 66% and 43% of the contralateral side, respectively. D1 and D2 receptor density in animals killed 10 days after injury was reduced by 24% and 22% of control, respectively, in striatum from brains with extensive damage. These results indicate complex changes in brain neuropeptides following neonatal hypoxia-ischemia. Damage in the substance P system could have functional effects on dopaminergic transmission while the increase in NPYLI and in DLI concentrations may respectively reflect the relative preservation from neuronal damage and possibly an increase in neuropeptide synthesis or decrease in release. The decrease in SPLI concentration and the increase DLI concentration induced by hypoxia-ischemia suggests that these peptides may be present in separate neurons.