title: NMDA and age dependent cerebral hemodynamics after traumatic brain injury.
abstract: 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.
authors.affiliation: Department of Anesthesia and Pharmacology, University of Pennsylvania, Philadelphia, PA 19104, USA. armsteaw@uphs.upenn.edu
authors.forename: William M
authors.initials: WM
authors.lastname: Armstead
mesh_terms: D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D001930:Brain Injuries / Q000503:physiopathology*; D002560:Cerebrovascular Circulation; D006801:Humans; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology*; D013552:Swine; D014664:Vasodilation
chemical_list: D016194:Receptors, N-Methyl-D-Aspartate