The role of opioids in newborn pig fluid percussion brain injury

The present study was designed to characterize the relationship between cerebral opioid concentration, cerebral hemodynamics, and cerebral oxygenation following percussion brain injury in neonatal pigs. Previous research found that opioids represent a significant vasoactive component in the regulation of the neonatal piglet cerebral circulation. Anesthesized newborn (1–5 days old) 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. Fluid percussion brain injury decreased pial arteriolar diameter (132 ± 5 to 110 ± 5 μm within 10 min). Cerebral blood flow also fell within 10 min of injury and continued to fall progressively for 3 h, resulting in a 46 ± 4% decrease. Within 30 s of brain injury, there was a transient increase in cerebral hemoglobin-O₂ saturation that was reversed to a progressive profound decrease in cerebral hemoglobin-O₂ saturation for the next 3 h, as measured by near infrared spectroscopy. CSF opioid concentrations were increased 10 min after brain injury; dynorphin showed the largest proportional increase (5.8 ± 0.9 fold). The CSF concentration for other opioids continued to increase over 180 min while the dynorphin concentration progressively decreased with time. In naloxone (1 mg/kg i.v.) pretreated piglets, the brain injury induced decrease in arteriolar diameter was attenuated (129 ± 5 to 121 ± 5 μm within 10 min). Similarly, the decrease in regional cerebral blood flow and cerebral hemoglobin-O₂ saturation observed following brain injury were also blunted by naloxone. These data show that CSF opioid concentrations increase following brain injury and that the time course and relative increase in CSF concentration vary from opioid to opioid. These data also indicate that in the immature animal, opioids contribute to arteriolar constriction, decreased cerebral blood flow, decreased cerebral oxygenation, and could play a role in causing ischemia after brain injury.