Smith S L, Hall E D
CNS Diseases Research, Upjohn Company, Kalamazoo, Michigan 49001, USA.
J Neurotrauma. 1996 Jan;13(1):1-9. doi: 10.1089/neu.1996.13.1.
Recent studies have demonstrated a neuroprotective effect of mild/moderate hypothermia in models of cerebral trauma and ischemia. In contrast, hypotension is known to exacerbate CNS injury. To better understand the mechanisms whereby hypothermia and hypotension influence secondary neural injury, the present study assessed the effects of these two variables upon blood-brain barrier (BBB) permeability following controlled cortical impact injury. Rats were subjected to either 0, 15, or 30 min of hypotension under normothermic or slightly hypothermic brain temperature conditions. Brain temperature was maintained within 0.5 degrees C of baseline (normothermic) or allowed to float freely (e.g., become hypothermic) throughout the study. Hypotension was induced immediately after head injury by rapid hemorrhage down to a mean arterial pressure of 50 mm Hg and held there for 15 or 30 min. Blood-brain barrier permeability was measured by the extravasation of plasma protein-bound Evan's blue dye into the injured cortex at 60 min postinjury. The results revealed that mild hypothermia (< 1.6 +/- 0.2 degrees C), right before and 15-30 min following head injury, significantly reduced BBB permeability 28.0, 21.8, and 26.2% in rats subjected to 0, 15, or 30 min hypotension, respectively (all p values < or = 0.05). Hypotension did not increase BBB permeability nor did it significantly interact with the brain temperature effect. Previous results, using this same model, have shown that the progressive posttraumatic increase in BBB permeability is preceded by an increase in cortical .OH and lipid hydroperoxides at the site of injury and is attenuated by the lipid peroxidation inhibitor tirilazad mesylate. Thus, the present results are discussed in terms of the role of free radical-induced lipid peroxidation in the genesis of posttraumatic BBB damage and the possible effects of hypothermia upon this injury process.
最近的研究表明，轻度/中度低温在脑外伤和缺血模型中具有神经保护作用。相比之下，已知低血压会加重中枢神经系统损伤。为了更好地理解低温和低血压影响继发性神经损伤的机制，本研究评估了这两个变量对控制性皮质撞击伤后血脑屏障（BBB）通透性的影响。在正常体温或轻度低温脑温条件下，对大鼠施加0、15或30分钟的低血压。在整个研究过程中，脑温维持在基线（正常体温）的0.5摄氏度范围内或使其自由浮动（例如，变为低温）。头部受伤后立即通过快速出血诱导低血压至平均动脉压50毫米汞柱，并维持15或30分钟。在受伤后60分钟，通过血浆蛋白结合的伊文思蓝染料渗入受伤皮质来测量血脑屏障通透性。结果显示，在头部受伤前及受伤后15 - 30分钟的轻度低温（< 1.6 +/- 0.2摄氏度），分别使经历0、15或30分钟低血压的大鼠的血脑屏障通透性显著降低28.0%、21.8%和26.2%（所有p值≤0.05）。低血压并未增加血脑屏障通透性，也未与脑温效应产生显著相互作用。使用相同模型的先前结果表明，创伤后血脑屏障通透性的逐渐增加之前，损伤部位的皮质.OH和脂质氢过氧化物会增加，并且脂质过氧化抑制剂甲磺酰替拉扎特可使其减弱。因此，本文根据自由基诱导的脂质过氧化在创伤后血脑屏障损伤发生中的作用以及低温对该损伤过程的可能影响来讨论当前结果。
