Henrich-Noack Petra, Striggow Frank, Reiser Georg, Reymann Klaus G
Institute for Neurobiochemistry, Otto-von-Guericke University Medical Faculty, Magdeburg, Germany.
J Neurosci Res. 2006 Feb 15;83(3):469-75. doi: 10.1002/jnr.20746.
The serine protease thrombin has shown direct neuroprotective and neurotoxic effects on brain tissue in cerebral ischemia. Previous data suggested that thrombin-induced protection in vivo can be achieved by preconditioning rather than by acute treatment. In the current work, we used a model of mild ischemia to investigate the effects of preischemic intracerebral thrombin injection on neural damage. By intracerebral injection of endothelin-1 in freely moving animals, we achieved middle cerebral artery occlusion (MCAO), and 7 days postischemia we performed histological quantification of the infarct areas. Thrombin was injected as a preconditioning stimulus intracerebrally 7 days or 2 and 3 days before ischemia. For acute treatment, thrombin was injected 20 min before MCAO. Thrombin induced significant neuroprotection when given 7 days before endothelin-1-induced MCAO but was deleterious when given 2 and 3 days before the insult. The deleterious effect was not seen when thrombin was given acutely before ischemia. Our data demonstrate that preconditioning with thrombin can protect against damage or worsen ischemic damage. Its effect depended on the time interval between thrombin injection and insult. A low dose of thrombin did not induce a major deleterious effect in the acute phase of the infarct development after mild transient ischemia.
丝氨酸蛋白酶凝血酶已显示出对脑缺血脑组织具有直接的神经保护和神经毒性作用。先前的数据表明，凝血酶在体内诱导的保护作用可通过预处理而非急性治疗来实现。在当前的研究中，我们使用轻度缺血模型来研究缺血前脑内注射凝血酶对神经损伤的影响。通过在自由活动的动物脑内注射内皮素-1，我们实现了大脑中动脉闭塞（MCAO），并在缺血7天后对梗死面积进行了组织学定量分析。在缺血前7天或2天及3天，将凝血酶作为预处理刺激物脑内注射。对于急性治疗，在MCAO前20分钟注射凝血酶。在内皮素-1诱导的MCAO前7天给予凝血酶可诱导显著的神经保护作用，但在损伤前2天和3天给予则具有有害作用。在缺血前急性给予凝血酶时未观察到有害作用。我们的数据表明，凝血酶预处理可预防损伤或加重缺血损伤。其效果取决于凝血酶注射与损伤之间的时间间隔。低剂量的凝血酶在轻度短暂性缺血后梗死发展的急性期不会诱导主要的有害作用。
