Inhibition of protein kinase Cβ reverses increased blood-brain barrier permeability during hyperglycemic stroke and prevents edema formation in vivo.
Inhibition of protein kinase Cβ reverses increased blood-brain barrier permeability during hyperglycemic stroke and prevents edema formation in vivo.
复制标题
抑制蛋白激酶 Cβ 可逆转高血糖脑卒中时血脑屏障通透性的增加，并防止体内水肿的形成。
DOI：
10.1161/strokeaha.111.623991
复制
发表时间：
2011-11
期刊：
影响因子：
8.3
通讯作者：
Sweet JG
中科院分区：
文献类型：
--
作者：
Cipolla MJ;Huang Q;Sweet JG
We investigated the effect of circulating factors and protein kinase Cβ (PKCβ) on blood-brain barrier permeability and edema during hyperglycemic stroke. Male Wistar rats that were hyperglycemic by streptozotocin (50 mg/kg) for 5–6 days underwent middle cerebral artery occlusion (MCAO) for 2 hours with 2 hours of reperfusion. Blood-brain barrier permeability was measured in MCAs that were ischemic (MCAO) or nonischemic (CTL) and perfused with plasma (20% in buffer) from MCAO or CTL animals. A separate set of MCAO vessels was perfused with the PKCβ inhibitor CGP53353 (0.5 μmol/L) and permeability measured. Lastly, hyperglycemic rats were treated i.v. with CGP53353 (10 or 100 μg/kg or vehicle 15 minutes prior to reperfusion and edema formation measured by wet:dry weights (n=6/group). MCAO vessels had increased permeability compared to controls, regardless of the plasma perfusate. Permeability (water flux, μm3 × 108) of CTL vessel/CTL plasma (n=8), CTL vessel/MCAO plasma (n=7), MCAO vessel/CTL plasma (n=6) and MCAO vessel/MCAO plasma (n=6) was 0.98±0.11, 1.13±0.07, 1.36±0.02, and 1.34±0.06; p<0.01). Inhibition of PKCβ in MCAO vessels (n=6) reversed the increase in permeability (0.92±0.1; p<0.01). In vivo, hyperglycemia increased edema vs. normoglycemia after MCAO (water content = 78.84±0.11% vs. 81.38±0.21%; p<0.01). Inhibition of PKCβ with 10 or 100 μg/kg CGP53353 during reperfusion prevented the increased edema in hyperglycemic animals (water content = 79.54±0.56% and 79.99±0.43%; p<0.01 vs. vehicle). These results suggest that the pronounced vasogenic edema that occurs during hyperglycemic stroke is mediated in large part by activation of PKCβ.
