Laboratory for Experimental Brain Research, Wallenberg Neuroscience Center, University of Lund, BMC A13, S-22184 Lund, Sweden.
Brain Res. 2010 Mar 19;1321:152-63. doi: 10.1016/j.brainres.2010.01.024. Epub 2010 Jan 18.
Elevated brain levels of apolipoprotein D (ApoD) correlate with improved neurological recovery after experimental stroke. Hence, a pharmacological induction of ApoD in the postischemic brain could be beneficial for recovery after stroke. Here we investigated the effect of Clozapine, a compound that increases the expression of ApoD, in two rat models of experimental stroke. Rats were subjected to permanent occlusion of the middle cerebral artery (pMCAO) and treated with Clozapine (i.p. 10 mg/kg body weight) or saline for 8 or 28 days starting on the second day after MCAO. ApoD levels increased by 35% in the peri-infarct area after 10 and 30 days after pMCAO, mainly in neuron-specific nuclear protein (NeuN) positive neurons and glial fibrillary acidic protein (GFAP) positive astrocytes. Clozapine did not affect the neurological deficit assessed by the rotating pole test and a grip strength test at 7 days, 14 days, 21 days, and 28 days after pMCAO. Functional outcome and the infarct size were similar in rats subjected to transient MCAO and injected with Clozapine (i.p. 10 mg/kg body weight) or saline for 26 days starting on the second day after tMCAO. We conclude that Clozapine affects cellular processes involved in peri-infarct tissue reorganization, but does not affect functional recovery after MCAO.
载脂蛋白 D（ApoD）脑水平升高与实验性中风后神经功能恢复改善相关。因此，在缺血后大脑中诱导 ApoD 的药物治疗可能有益于中风后的恢复。在此，我们研究了氯氮平（一种增加 ApoD 表达的化合物）在两种实验性中风大鼠模型中的作用。大鼠接受大脑中动脉永久性闭塞（pMCAO），并在 MCAO 后第 2 天开始，每天腹腔注射氯氮平（10mg/kg 体重）或生理盐水 8 或 28 天。pMCAO 后 10 天和 30 天，在梗死周边区，ApoD 水平增加了 35%，主要在神经元特异性核蛋白（NeuN）阳性神经元和神经胶质纤维酸性蛋白（GFAP）阳性星形胶质细胞中增加。氯氮平在 pMCAO 后 7 天、14 天、21 天和 28 天通过旋转杆试验和握力试验评估神经功能缺损时没有影响。在接受短暂性大脑中动脉闭塞（tMCAO）并在 tMCAO 后第 2 天开始每天腹腔注射氯氮平（10mg/kg 体重）或生理盐水 26 天的大鼠中，功能结局和梗死体积相似。我们得出结论，氯氮平影响梗死周边组织重构过程中的细胞过程，但不影响 MCAO 后的功能恢复。
