Age dependent NMDA contribution to impaired hypotensive cerebral hemodynamics following brain injury.
Previous studies have observed that fluid percussion brain injury (FPI) impaired NMDA induced pial artery dilation (PAD) in an age dependent manner. Unrelated studies observed a similar age dependent impairment of hypotensive cerebral autoregulation after FPI. This study was designed to test the hypothesis that NMDA receptor activation contributes to impairment of cerebral autoregulation during hypotension after FPI in an age dependent manner. Therefore, the role of NMDA in impaired hypotensive cerebrovascular regulation after FPI was compared in newborn and juvenile pigs equipped with a closed cranial window. Ten minutes of hypotension (10-15 ml blood/kg) decreased mean arterial blood pressure uniformly in both groups (approximately 44%). In the newborn, hypotensive PAD was blunted within 1 h of FPI but partially protected by pretreatment with the NMDA antagonist MK801 (1 mg/kg i.v.) (34+/-1 vs. 8+/-1 vs. 25+/-2% for sham control, FPI, and FPI-MK801, respectively). Cerebral blood flow (CBF) was reduced during normotension by FPI, further reduced by hypotension, but both were partially protected by MK801 in the newborn (56+/-5, 35+/-2, and 16+/-1 vs. 62+/-6, 45+/-3, and 30+/-2 ml/min 100 g for normotension, normotension-FPI, and hypotension-FPI in the absence and presence of MK801, respectively). In contrast, blunted hypotensive PAD was protected significantly less by MK801 in the juvenile (32+/-2 vs. 7+/-2 vs. 16+/-2% for sham control, FPI, and FPI-MK801, respectively). 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 brain injury in an age dependent manner.
Armstead
William M
WM
Department of Anesthesia, University of Pennsylvania, 3400 Spruce Street, Philadelphia, PA 19104, USA. armsteaw@uphs.upcnn.edu
D000375:Aging / Q000378:metabolism*; D000818:Animals; D000831:Animals, Newborn; D001774:Blood Chemical Analysis; D001930:Brain Injuries / Q000503:physiopathology*; D002536:Cerebral Arteries / Q000502:physiology; D002560:Cerebrovascular Circulation / Q000502:physiology*; D016291:Dizocilpine Maleate / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005260:Female; D006706:Homeostasis / Q000502:physiology; D007022:Hypotension / Q000503:physiopathology*; D008297:Male; D008863:Microspheres; D016202:N-Methylaspartate / Q000378:metabolism*; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000378:metabolism; D013552:Swine
D018691:Excitatory Amino Acid Antagonists; D016194:Receptors, N-Methyl-D-Aspartate; D016202:N-Methylaspartate; D016291:Dizocilpine Maleate