Analysis of ischemic tolerance in view of neurotrophic factors

已知皮质扩散抑制(CSD)可在大鼠脑缺血模型中诱导缺血耐受。CSD在局灶性脑缺血模型中减少脑梗塞体积，在全脑缺血模型中减轻海马神经元损伤，当在这些侮辱前3天被激发时。最近，脑源性神经营养因子(BDNF)在活体模型中被证明具有保护神经元免受各种损伤的作用。因此，本研究探讨了CSD诱导的大鼠缺血耐受与脑源性神经营养因子表达的关系。用氯化钾溶液浸泡大脑皮层1h，诱导CSD。Northern印迹和原位杂交研究表明，CSD动物在4h和3d时，同侧大脑皮质中的mRNA表达显著上调，而在对照动物中则没有。在海马区，没有观察到可检测到的变化。蛋白质水平分析采用BDNF-EL ISA法。这项研究表明，在CSD后12小时和3天，BDNF蛋白在同侧皮质也增加，但在海马区没有增加。脑源性神经营养因子MNA和蛋白表达的增加在时间上与大脑皮层缺血耐受的诱导相一致，而在海马区则不是。提示脑源性神经营养因子的增加可能参与了大脑皮层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.