We have previously shown that following 3 hrs of H-I at 31, 34, or 37°C; 0, 40, and 90% of 7-day rat pups respectively displayed brain damage(Ped Res.29:366,1991). This effect is only partially explained by a preservation of high-energy phosphates in the 31°C group, since ATP is equally depleted in the 34 and 37°C groups (Can.J.Neurol.Sci. 21:S48, 1994). To further investigate the mechanisms underlying the neuroprotective effect of mild hypothermia, in vivo microdialysis was utilized to determine hippocampal amino acid (AA) efflux during H-I. 7-day rats underwent unilateral common carotid artery ligation and exposure to hypoxia in 8% oxygen for 3 hours at either 31, 34, or 37°C. Microdialysis probes (CMA 11) were placed in the ipsilateral CA1 region of the hippocampus, and dialysate collected for 20 min. at 1 hr prior to, and at 60, 120, and 180 min during H-I. Samples were immediately analyzed for alanine, glutamine, glutamate, glycine, taurine, serine, and GABA by high-performance liquid chromatography with electrochemical detection. Prior to H-I, there were no differences between groups in extracellular AA concentrations. During H-I, the concentrations of all AA, except glutamine, rose significantly above control values (p<0.001) only in the 37°C group. In the 34°C group, only alanine increased above control (p<0.01), whereas the other AA remained within control limits. No increases in AA levels were seen in the 31°C group. Thus, 1) The mechanism of protection by mild hypothermia is temperature dependant, 2) Mild hypothermia of 34°C exerts its protective effect by suppressing excitatory AA release, and 3) excess alanine in the extracellular fluid may be a sensitive indicator of brain injury in the immature rat.(Supported by the Heart & Stroke Foundation of Saskatchewan).
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(Spon. by Koravangattu Sankaran).
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Yager, J., Armstrong, E. EFFECTS OF MILD HYPOTHERMIA ON AMINO ACID EFFLUX DURING HYPOXIA-ISCHEMIA(H-I) IN THE IMMATURE RAT. † 2281. Pediatr Res 39 (Suppl 4), 383 (1996). https://doi.org/10.1203/00006450-199604001-02306
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DOI: https://doi.org/10.1203/00006450-199604001-02306