Matrix metalloproteinases and TIMPs are associated with blood-brain barrier opening after reperfusion in rat brain
Matrix metalloproteinases and TIMPs are associated with blood-brain barrier opening after reperfusion in rat brain
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DOI：
10.1161/01.str.29.10.2189
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发表时间：
1998-10-01
期刊：
影响因子：
8.3
通讯作者：
Dencoff, JE
中科院分区：
文献类型：
--
作者：
Rosenberg, GA;Estrada, EY;Dencoff, JE
背景和目的-再灌注破坏脑毛细血管，引起脑水肿和出血。大脑中动脉闭塞（MCAO）诱导基质降解金属蛋白酶，但其在再灌注后毛细血管损伤中的作用尚不清楚。基质金属蛋白酶（MMPs）和组织金属蛋白酶抑制剂（TTMPs）调节毛细血管通透性。因此，我们测量血脑屏障（BBB）的通透性，脑水和电解质，MMPs，和TIMPs在多个时间后reperfusion. Methods成年大鼠进行MCAO 2小时的缝合方法。在再灌注后3小时至14天测定脑对C-14-蔗糖的摄取。分别用酶谱法和反向酶谱法测定邻近组织中MMPs和TIMPs的水平。其他大鼠在再灌注后3、24或48小时测量水和电解质。治疗与合成MMP抑制剂，BB-1101，对血脑屏障通透性和脑水肿studied.Results-Brain蔗糖摄取增加后3和48小时的再灌注，最大开放时间为48小时，并恢复到正常的14天。3小时明胶酶A水平与蔗糖吸收量呈显著正相关（P
Background and Purpose-Reperfusion disrupts cerebral capillaries, causing cerebral edema and hemorrhage. Middle cerebral artery occlusion (MCAO) induces the matrix-degrading metalloproteinases, but their role in capillary injury after reperfusion is unknown. Matrix metalloproteinases (MMPs) and tissue inhibitors to metalloproteinases (TTMPs) modulate capillary permeability. Therefore, we measured blood-brain barrier (BBB) permeability, brain water and electrolytes, MMPs, and TIMPs at multiple times after reperfusion.Methods-Adult rats underwent MCAO for 2 hours by the suture method. Brain uptake of C-14-sucrose was measured from 3 hours to 14 days after reperfusion, Levels of MMPs and TIMPs were measured by zymography and reverse zymography, respectively, in contiguous tissues. Other rats had water and electrolytes measured at 3, 24, or 48 hours after reperfusion. Treatment with a synthetic MMP inhibitor, BB-1101, on BBB permeability and cerebral edema was studied.Results-Brain sucrose uptake increased after 3 and 48 hours of reperfusion, with maximal opening at 48 hours and return to normal by 14 days. There was a correlation between the levels of gelatinase A at 3 hours and the sucrose uptake (P