Effects of rapamycin pretreatment on blood-brain barrier disruption in cerebral ischemia-reperfusion

被引:32
作者
Chi, Oak Z. [1 ]
Mellender, Scott J. [1 ]
Barsoum, Sylviana [1 ]
Liu, Xia [1 ]
Damito, Stacey [2 ]
Weiss, Harvey R. [2 ]
机构
[1] Rutgers Robert Wood Johnson Med Sch, Dept Anesthesiol, 125 Paterson St,Suite 3100, New Brunswick, NJ 08901 USA
[2] Rutgers Robert Wood Johnson Med Sch, Dept Neurosci & Cell Biol, New Brunswick, NJ 08901 USA
关键词
mTOR; Rapamycin; BBB permeability; Cerebral ischemia-reperfusion; Cerebral infarction; Neuroprotection; MAMMALIAN TARGET; INJURY; RAT; STROKE; CONTRIBUTES; ACTIVATION; INTEGRITY; PATHWAY; INDUCE; MICE;
D O I
10.1016/j.neulet.2016.03.053
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
The mammalian target of rapamycin (mTOR) pathway is essential in neuronal survival and repair in cerebral ischemia. Decreases in blood-brain barrier (BBB) disruption are associated with a decrease in neuronal damage in cerebral ischemia. This study was performed to investigate how pre-inhibition of the mTOR pathway with rapamycin would affect BBB disruption and the size of the infarcted cortical area in the early stage of focal cerebral ischemia-reperfusion using quantitative analysis of BBB disruption. Rats were treated with 20 mg/kg of rapamycin i.p. once a day for 2 days (Rapamycin Group) or vehicle (Control Group) before transient middle cerebral artery (MCA) occlusion. After one hour of MCA occlusion and two hours of reperfusion, the transfer coefficient (IQ of C-14-alpha-aminoisobutyric acid (C-14-AIB) to measure the degree of BBB disruption and the size of the cortical infarct were determined. Ischemia-reperfusion increased the K-i in the Rapamycin treated (+15%) as well as in the untreated control group (+13%). However, rapamycin pretreatment moderately decreased Ki in the contralateral (-30%) as well as in the ischemic-reperfused (-29%) cortex when compared with the untreated control group. Rapamycin pretreatment substantially increased the percentage of cortical infarct compared with the control group (+56%). Our data suggest that activation of mTOR pathway is necessary for neuronal survival in the early stage of cerebral ischemia-perfusion and that the reason for the enlarged cortical infarct by rapamycin pretreatment may be related to its non-BBB effects on the mTOR pathway. (C) 2016 Elsevier Ireland Ltd. All rights reserved.
引用
收藏
页码:132 / 136
页数:5
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