Activation of
N-methyl-D-aspartate (
NMDA) glutamatergic receptors elicits cerebrovascular dilation, may couple local cerebral metabolism to blood flow but contribute to excitotoxic neuronal cell death. While cerebral hemodynamics following
traumatic brain injury may correlate with neurologic status, the role of
NMDA vascular activity is uncertain in the sequelae of
brain injury.
NMDA dilation was impaired following fluid percussion
brain injury (FPI) in an age dependent manner in the pig and the newly described
opioid nociceptin/orphanin FQ (NOC/ oFQ) contributes to such impairment via the
cyclooxygenase dependent generation of
superoxide. Further, hypotensive pial artery dilation (PAD) was blunted after FPI but partially protected by pretreatment with the
NMDA antagonist
MK801. Cerebral blood flow (CBF) was reduced during normotension by FPI, further reduced by
hypotension, but both were partially protected by
MK801 in the newborn. In contrast, blunted hypotensive PAD was protected significantly less by
MK801 in the juvenile pig. Similarly,
MK801 had less protective effect on normotensive and hypotensive CBF values post FPI in the juvenile. These data indicate that
NMDA receptor activation contributes to impaired hypotensive cerebral hemodynamics following FPI in an age dependent manner. Further, these data suggest that
NMDA receptor activation, NOC/oFQ, and
prostaglandins dynamically interact to impair cerebral hemodynamics following FPI.