Truettner Jessie S, Alonso Ofelia F, Dietrich W Dalton
Department of Neurological Surgery, Neurotrauma Research Center, The Miami Project to Cure Paralysis, University of Miami School of Medicine, Miami, Florida 33101, USA.
J Cereb Blood Flow Metab. 2005 Nov;25(11):1505-16. doi: 10.1038/sj.jcbfm.9600150.
Recent evidence suggests that matrix metalloproteinases (MMPs) contribute to acute edema and lesion formation following ischemic and traumatic brain injuries (TBI). Experimental and clinical studies have also reported the beneficial effects of posttraumatic hypothermia on histopathological and behavioral outcome. The purpose of this study was to determine whether therapeutic hypothermia would affect the activity of MMPs after TBI. Male Sprague-Dawley rats were traumatized by moderate parasagittal fluid-percussion (F-P) brain injury. Seven groups (n=5/group) of animals were investigated: sham-operated, TBI with normothermia (37 degrees C), and TBI with hypothermia (33 degrees C). Normothermia animals were killed at 4, 24, 72 h and 5 days, and hypothermia animals at 24 or 72 h. Brain temperature was reduced to target temperature 30 mins after trauma and maintained for 4 h. Ipsilateral and contralateral cortical, hippocampal, and thalamic regions were analyzed by gelatin and in situ zymography. In traumatized normothermic animals, TBI significantly (P<0.005) increased MMP-9 levels in ipsilateral (right) cortical and hippocampal regions, compared with contralateral or sham animals, beginning at 4 h and persisting to 5 days. At 1, 3, and 5 days after TBI, significant increases in MMP-2 levels were observed. In contrast to these findings observed with normothermia, posttraumatic hypothermia significantly reduced MMP-9 levels. Hypothermic treatment, however, did not affect the delayed activation of MMP-2. Clarifying the mechanisms underlying the beneficial effects of posttraumatic hypothermia is an active area of research. Posttraumatic hypothermia may attenuate the deleterious consequences of brain trauma by reducing MMP activation acutely.
近期证据表明，基质金属蛋白酶（MMPs）在缺血性脑损伤和创伤性脑损伤（TBI）后会导致急性水肿和损伤形成。实验和临床研究也报道了创伤后低温对组织病理学和行为结果的有益影响。本研究的目的是确定治疗性低温是否会影响TBI后MMPs的活性。雄性Sprague-Dawley大鼠通过中度矢状旁流体冲击（F-P）脑损伤致伤。研究了七组动物（每组n = 5）：假手术组、常温（37℃）TBI组和低温（33℃）TBI组。常温动物在4、24、72小时和5天时处死，低温动物在24或72小时时处死。创伤后30分钟将脑温降至目标温度并维持4小时。通过明胶和原位酶谱分析同侧和对侧皮质、海马和丘脑区域。在创伤后的常温动物中，与对侧或假手术动物相比，TBI在同侧（右侧）皮质和海马区域显著（P<0.005）增加了MMP-9水平，从4小时开始并持续至5天。在TBI后1、3和5天，观察到MMP-2水平显著升高。与常温下观察到的这些结果相反，创伤后低温显著降低了MMP-9水平。然而，低温治疗并未影响MMP-2的延迟激活。阐明创伤后低温有益作用的潜在机制是一个活跃的研究领域。创伤后低温可能通过急性降低MMP激活来减轻脑损伤的有害后果。
