Effects of Alkalizing Agents (THAM) on Ischemic Brain Injuries

[目的]探讨亚低温下碱化剂（THAM：三羟甲基氨基甲烷）对急性硬膜下血肿大鼠脑损伤及血脑屏障（BBB）通透性的影响。[方法]成年雄性SD大鼠随机分为4个实验组：（a）常温组（37℃），（B）亚低温组（35℃），（c）THAM组，（d）亚低温+THAM组。在诱导硬膜下血肿后4 h测量脑皮质含水量、脑梗死体积和血脑屏障通透性。[结果]单纯亚低温组血肿下脑水肿形成率（79.5±0.2%）与常温组（80.2±0.2%）相比无显著性差异。然而，与常温相比，THAM治疗显著减少脑水肿形成（79.0±0.1% ; p<0.05）。这种降低与轻度低温相结合是显著的（78.7±0.0% ; p<0.05）。与常温治疗（59± 3 mm 3）相比，诱导亚低温（51± 3 mm 3：p<0.05）、THAM治疗（49± 3 mm 3：p<0.05）和诱导亚低温联合THAM治疗（46± 3 mm 3：p<0.01）显著减小脑梗死体积。与常温（63± 7 ng/g湿组织）相比，与两种治疗组合显著降低了BBB破坏（35± 7 ng/g湿组织：p<0.05）。[结论] 35℃亚低温联合THAM具有明显的神经保护作用。BBB的保护是该大鼠急性SDH模型中可能的神经保护机制之一。

【 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.