Analysis of ischemic tolerance in view of neurotrophic factors

皮质扩散性抑制（CSD）在大鼠脑缺血模型中可诱导缺血耐受。CSD减少局灶性缺血模型中的脑梗死体积，并在全脑缺血模型中减弱海马神经元损伤，当在这些损伤前3天引起时。最近，脑源性神经营养因子（BDNF）已被证明可以保护神经元免受各种损伤在体内模型。因此，本研究探讨了CSD诱导的大鼠脑缺血耐受与BDNF表达的关系。通过将KCl溶液施加到皮层上1小时来诱导CSD。北方杂交和原位杂交结果显示，CSD组大鼠同侧皮层mRNA表达在4 h和3 d时呈双相性上调，而对照组无明显变化。在海马体中，未观察到可检测的变化。为了分析蛋白水平，进行BDNF ELISA测定。本研究显示，在CSD后12小时和3天，同侧皮质中BDNF蛋白也增加，但海马中没有。脑源性神经营养因子mRNA和蛋白的增加与皮层缺血耐受的诱导时间一致，但在海马中不一致。提示脑源性神经营养因子的增加可能参与了脑缺血耐受的内源性机制。

Cortical spreading depression(CSD)is known to induce ischemic tolerance in a rat model of cerebral ischemia. CSD reduces volume of cerebral infarction in a focal ischemia model and attenuates hippocampal neuronal injury in a global ischemia model, when elicited 3 days prior to these insults. Recently, brain-derived neurotrophic factor(BDNF)has been shown to protect neurons against various insults in in vivo model. This study, therefore, investigated relationship between CSD-induced ischemic tolerance and expression of BDNF in rats. CSD was induced by applying KCl solution onto the cortex for 1 hour. For control animals, NaCl solution was used.Northern blot and in situ hybridization study showed that mRNA was dramatically upregulated biphasically in the ipsilateral cortex at 4 hours and 3 days in the CSD animals, but not in the controls. In the hippocampus, no detectable changes were not observed. For analysis of protein level, BDNF ELISA assay was performed. This study revealed that BDNF protein was also increased at 12 hours and 3 days post CSD in the ipsilateral cortex, but not in the hippocampus. The increase of BDNF mNA and protein coincided in time with the induction of ischemic tolerance in the cortex, but not in the hippocampus. These results suggested that increase of BDNF may be involved in the mechanism of endogenous mechanism of ischemic tolerance in the cortex.