RELATIONSHIP BETWEEN OPIOIDS AND ACTIVATION OF PHOSPHOLIPASE-C AND PROTEIN-KINASE-C IN BRAIN INJURY-INDUCED PIAL ARTERY VASOCONSTRICTION

Previously, it has been observed that newborn pig pial artery constric tion after fluid percussion brain injury was associated with elevated CSF dynorphin and beta endorphin concentration. Additionally, brain in jury reversed dynorphin-induced pial artery vasodilation to vasoconstr iction. The present study was designed to characterize the relationshi p between opioids and activation of phospholipase C (PLC) and protein kinase C (PKC) in brain injury-induced pial vasoconstriction. Anesthet ized newborn pigs equipped with a closed cranial window were connected to a percussion device consisting of a saline-filled cylindrical rese rvoir with a metal pendulum. Brain injury of moderate severity (1.9-2. 3 atm) was produced by allowing the pendulum to strike a piston on the cylinder. Brain injury decreased pial arteriolar diameter within 10 m in of injury and continued to fall progressively for 3 h (130 +/- 5, 1 08 +/- 4 and 102 +/- 5 mu m for 0, 10 and 180 min postinjury). In cont rast, the PLC inhibitor, neomycin (10(-4) M), blunted brain injury-ind uced pial vasoconstriction (133 +/- 4, 129 +/- 4 and 135 +/- 5 mu m fo r 0, 10 and 180 min postinjury, respectively). Similarly, staurosporin e (10(-7) M), a PKC inhibitor, also blunted brain injury-induced vasoc onstriction. beta endorphin (10(-8), 10(-6) M)-induced pial artery vas oconstriction was blunted by neomycin (12 +/- 1, 19 +/- 1 vs. 2 +/- 1, 4 +/- 2% constriction before and after neomycin, respectively). Staur osporine similarly blunted beta endorphin pial constriction (10 +/- 1, 15 +/- 1 vs. 1 +/- 1, 1 +/- 1% constriction before and after staurosp orine, respectively). The constrictor potential for dynorphin was also inhibited by neomycin and staurosporine. These data indicate that bra in injury-induced pial artery constriction is mediated, at least in pa rt, by activation of PLC and PKC. Further, since CSF dynorphin and bet a endorphin concentrations are increased after brain injury, these dat a suggest that these two opioids contribute to activation of PLC and P KC observed after brain injury.