Effects of Alkalizing Agents (THAM) on Ischemic Brain Injuries

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【 Objectives 】In this study, we attempted to evaluate the effects of alkalizing agents (THAM : tris (hydroxymetyl) aminomethane) under mild hypothermia on brain injury and the blood brain barrier (BBB) permeability after acute subdural hematoma in rats. 【 Methods 】Adult male Sprague-Dawley rats were divided into four experimental groups, as follows : (a) normothermia group (37℃ ), (b) mild hypothermia group (35℃ ), (c) THAM group, (d) mild hypothermia+THAM group. The cortical brain water content, cerebral infarct volume, and BBB permeability were measured at 4 hours after the induction of subdural hematoma. 【 Results 】Mild hypothermia alone did not significantly reduce brain edema formation underneath the hematoma (79.5±0.2%) compared with the normothermia (80.2±0.2%). THAM treatment, however, significantly reduced the brain edema formation (79.0±0.1% ; p<0.05) compared with the normothermia. This reduction was dramatic combined with mild hypothermia (78.7±0.0% ; p<0.05). Cerebral infarct volume was significantly reduced by inducing mild hypothermia (51±3mm3 : p<0.05), by THAM treatment (49±3mm3 : p<0.05) and by inducing mild hypothermia combined with THAM treatment (46±3mm3 : p<0.01) in comparison with the normothermic treatment (59±3mm3). Combined with both treatment significantly reduced the BBB breakdown (35±7ng/g wet tissue : p<0.05) compared with normothermia (63±7ng/g wet tissue). 【Conclusion】The present findings indicate that mild hypothermia of 35℃ combined with THAM presents a potent neuroprotective strategy. The protection of the BBB is one of the possible neuroprotective mechanisms in this rat acute SDH model.