Investigation into the cross-talk of cell adhesion molecule in the brain on the mechanism, of neuronal protection

我们一直在研究血浆纤维连接蛋白（pFn）对局灶性脑缺血的影响，直到2001年，我们发现pFn支持神经元存活，减少短暂局灶性脑缺血后的脑损伤，并通过TUNEL和caspaseS的测量识别出抗凋亡作用，因此我们开始了环孢素（CsA）对小鼠局灶性脑缺血的影响的研究。从而研究pFn的抗凋亡作用。然而，CsA不被血脑屏障（BBB）渗透，我们使用的mdrla敲除小鼠没有CsA从脑向血液的主动外排。我们发现CsA对小鼠短暂性局灶性脑缺血有抗缺血作用。相反，CsA也表现出神经毒性作用，且CsA剂量不同，mdrla基因敲除小鼠未经CsA处理的waa梗死面积明显大于野生型小鼠，提示mdrla可能对脑缺血后的脑损伤有效。

We had been investigating the effect of plasma fihronectin(pFn) to focal cerebral ischemia using the conditional knockout mouse which is pFn deficient until 2001, We found that pFn supports neuronal survival and reduces brain injury following transient focal cerebral ischemia with anti-apoptotic effect which were recognized by the measurement of TUNEL and caspaseS and so oa We have started the study which is the effect of cyclosporinA(CsA) to focal cerebral ischemia on mice, leading to the research of pFn anti-apoptotic effect. CsA, however, is impermeable by blood-brain barrier(BBB), and we used mdrla knockout mice which don't have the active efflux of CsA from brain to blood. We found that CsA demonstrated the anti-ischenaic effect on the mice following following transient focal cerebral ischemia. On the contrary, CsA also showed the neurotoxic effect, depending on dosage of CsA Additionally, the infarct volume of mdrla knockout mice without CsA-treated waa significantly bigger than that of wild-type mice, suggesting that mdrla may be effective to brain injury after transient ischemia.