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大鼠大脑皮层局灶性梗死和消融后急性期对侧丘脑紧密连接完整性降低。

Decrease of tight junction integrity in the ipsilateral thalamus during the acute stage after focal infarction and ablation of the cerebral cortex in rats.

机构信息

Department of Neurology and Stroke Center, First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China.

出版信息

Clin Exp Pharmacol Physiol. 2011 Nov;38(11):776-82. doi: 10.1111/j.1440-1681.2011.05591.x.

Abstract
  1. Whether damage to the blood-brain barrier (BBB) occurs in remote areas after a focal cortical lesion remains unknown. The present study investigated tight junction-related proteins and tight junction microstructure in the ipsilateral thalamus during the acute stage after middle cerebral artery occlusion (MCAO) and cortical aspiration lesion (CAL) in rats. 2. Thirty-six hypertensive and normotensive rats were subjected to MCAO or CAL; another 18 rats in each group were submitted to sham operation. Zonula Occluden (ZO)-1, occludin and albumin were detected by western blotting 12 and 24 h after surgery. Tight junction microstructure was evaluated using electron microscopy, whereas albumin location in the ipsilateral thalamus was determined using double immunostaining for albumin and occludin or albumin and neuronal nuclei (NeuN) 24 h after surgery. 3. Twenty-four hours after MCAO or CAL, occludin expression was reduced to 78.4% and 81.3%, respectively, compared with control. A reduction in ZO-1 expression in the ipsilateral thalamus (to 79%) was seen only after CAL (P < 0.05). Membrane contact at the tight junction was discontinuous in the ipsilateral thalamus in both MCAO and CAL rats. Albumin levels were 23.2% and 82.5% higher in the ipsilateral thalamus after MCAO and CAL, respectively (P < 0.05). The percentage of the albumin-positive area that coincided with the occludin-positive area in the MCAO and CAL groups was 76.8% and 64.6%, respectively, indicating that albumin was mainly localized around the microvessels. 4. The results of the present study suggest that tight junction integrity decreases during the acute stage in the ipsilateral thalamus after MCAO and CAL in rats.
摘要
  1. 局灶性皮质损伤后,血脑屏障(BBB)是否在远隔部位受损尚不清楚。本研究在大鼠大脑中动脉闭塞(MCAO)和皮质抽吸损伤(CAL)后急性期,观察了对侧丘脑紧密连接相关蛋白和紧密连接超微结构的变化。

  2. 36 只高血压和正常血压大鼠接受 MCAO 或 CAL;每组另外 18 只大鼠接受假手术。术后 12 和 24 h 时,采用 Western blot 法检测紧密连接蛋白 ZO-1、occludin 和白蛋白。电镜观察紧密连接超微结构,术后 24 h 时采用白蛋白和 occludin 或白蛋白和神经元核(NeuN)双重免疫荧光法检测对侧丘脑内白蛋白定位。

  3. MCAO 或 CAL 后 24 h,occludin 表达分别降至对照组的 78.4%和 81.3%。仅在 CAL 后,对侧丘脑 ZO-1 表达减少至 79%(P<0.05)。MCAO 和 CAL 大鼠对侧丘脑紧密连接的膜接触不连续。MCAO 和 CAL 后,对侧丘脑白蛋白水平分别升高 23.2%和 82.5%(P<0.05)。MCAO 和 CAL 组白蛋白阳性区与 occludin 阳性区重合的百分比分别为 76.8%和 64.6%,表明白蛋白主要定位于微血管周围。

  4. 本研究结果表明,大鼠 MCAO 和 CAL 后急性期对侧丘脑紧密连接完整性降低。

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