Therapeutic hypothermia is cytoprotective without attenuating the traumatic brain injury-induced elevations in interstitial concentrations of aspartate and glutamate.
Moderate hypothermia has been shown to have therapeutic utility in the treatment of cerebral ischemia and to attenuate the rise in interstitial concentrations of the excitatory amino acid neurotransmitter L-glutamate. In this study, the influence of hypothermia on traumatic brain injury (TBI) was assessed using a controlled cortical impact model. Rats were cooled to 32.0-33.0 degrees C at least 30 min before injury and maintained at this temperature for 2 h after injury. The influence of hypothermia on the immediate increase in interstitial concentrations of aspartate and glutamate and the volume of the resultant lesion 14 days after TBI was then determined. The volume of the lesion (mean +/- SEM) in hypothermic animals (8.2 +/- 1.3 mm3, n = 9) was significantly smaller than that of normothermic animals (13.2 +/- 1.7 mm3, n = 8). By contrast, TBI-induced increases in dialysate concentrations of aspartate and glutamate were similar at the two temperatures. Thus, aspartate content (nmol/10 min) in animals maintained at 37.0-37.5 degrees C (n = 6) and 32.0-33.0 degrees C (n = 6) increased from respective mean preinjury values of 0.05 +/- 0.02 and 0.08 +/- 0.02 to much larger peak values (0.78 +/- 0.13 and 0.71 +/- 0.09, respectively). Similarly, under normothermic conditions glutamate content (nmol/10 min) increased from 0.13 +/- 0.03 to 3.08 +/- 0.52 and from 0.19 +/- 0.06 to a peak value of 3.09 +/- 0.26 under hypothermic conditions. These data clearly demonstrate the cytoprotective action of moderate hypothermia and further suggest that this action is not mediated by attenuation of the rise in interstitial concentrations of aspartate and glutamate.
Palmer
A M
AM
Department of Psychiatry, University of Pittsburgh School of Medicine, Pennsylvania.
Marion
D W
DW
Botscheller
M L
ML
Redd
E E
EE
D000596:Amino Acids / Q000032:analysis; D000818:Animals; D001224:Aspartic Acid / Q000378:metabolism*; D001921:Brain / Q000473:pathology; D001930:Brain Injuries / Q000378:metabolism* / Q000473:pathology / Q000628:therapy*; D002851:Chromatography, High Pressure Liquid; D005971:Glutamates / Q000378:metabolism*; D018698:Glutamic Acid; D006651:Histocytochemistry; D007036:Hypothermia, Induced; D008297:Male; D017551:Microdialysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D013050:Spectrometry, Fluorescence
D000596:Amino Acids; D005971:Glutamates; D001224:Aspartic Acid; D018698:Glutamic Acid