Relationship between opioids and activation of phospholipase C and protein kinase C in brain injury induced pial artery vasoconstriction

Abstract

Previously, it has been observed that newborn pig pial artery constriction after fluid percussion brain injury was associated with elevated CSF dynorphin and β endorphin concentration. Additionally, brain injury reversed dynorphin-induced pial artery vasodilation to vasoconstriction. The present study was designed to characterize the relationship between opioids and activation of phospholipase C (PLC) and protein kinase C (PKC) in brain injury-induced pial vasoconstriction. Anesthetized newborn pigs equipped with a closed cranial window were connected to a percussion device consisting of a saline-filled cylindrical reservoir 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 min of injury and continued to fall progressively for 3 h (130 ± 5, 108 ± 4 and 102 ±5 μm for 0, 10 and 180 min postinjury). In contrast, the PLC inhibitor, neomycin (10 −4 M), blunted brain injury-induced pial vasoconstriction (133 ± 4, 129 ± 4 and 135 ± 5 μm for 0, 10 and 180 min postinjury, respectively). Similarly, staurosporine (10 −7 M), a PKC inhibitor, also blunted brain injury-induced vasoconstriction. β endorphin (10 −8, 10 −6 M)-induced pial artery vasoconstriction was blunted by neomycin (12 ± 1, 19 ± 1 vs. 2 ± 1, 4 ± 2% constriction before and after neomycin, respectively. Staurosporine similarly blunted β endorphin pial constriction (10 ± 1, 15 ± 1 vs. 1 ± 1, 1 ± 1 % constriction before and after staurosporine, respectively). The constrictor potential for dynorphin was also inhibited by neomycin and staurosporine. These data indicate that brain injury-induced pial artery constriction is mediated, at least in part, by activation of PLC and PKC. Further, since CSF dynorphin and β endorphin concentrations are increased after brain injury, these data suggest that these two opioids contribute to activation of PLC and PKC observed after brain injury.