Isoflurane-Induced Postoperative Neurovascular and Cognitive Dysfunction Is Associated with VEGF Overexpression in Aged Rats
Isoflurane-Induced Postoperative Neurovascular and Cognitive Dysfunction Is Associated with VEGF Overexpression in Aged Rats
复制标题
异氟烷诱导的术后神经血管和认知功能障碍与老年大鼠 VEGF 过度表达相关
DOI：
10.1007/s12031-019-01350-8
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发表时间：
2019-10-01
影响因子：
3.1
通讯作者：
Guo, Xiangyang
中科院分区：
文献类型：
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作者：
Cao, Yiyun;Li, Zhengqian;Guo, Xiangyang
术后认知功能障碍（POCD）是老年人常见的并发症;然而，其病因尚不清楚。虽然血管内皮生长因子（VEGF）与血脑屏障（BBB）障碍和神经系统疾病有关，但其在POCD中的作用尚不清楚。在这里，我们研究了在老年大鼠POCD模型中抑制脑VEGF对异氟醚诱导的认知障碍的影响。VEGF蛋白表达增加后，异氟醚暴露在海马，表明吸入麻醉诱导老年大鼠海马VEGF蛋白过表达。用2 mg/kg RB-222（一种抗VEGF中和抗体）预处理可部分消除脑毛细血管中occludin蛋白的降解，从而维持海马BBB的超微结构和功能完整性。VEGF的抑制也显着减弱了异氟烷诱导的认知障碍，在Morris水迷宫任务。总之，我们的研究结果首次表明，异氟烷暴露后脑VEGF的表达升高有助于老年大鼠的POCD。因此，涉及VEGF的治疗策略应考虑其在POCD发病机制中的作用。
Postoperative cognitive dysfunction (POCD) is a common complication in older adults; however, its aetiology remains unclear. Although vascular endothelial growth factor (VEGF) is associated with blood-brain barrier (BBB) disorders and neurological disease, its role in POCD is unknown. Here, we investigated the effect of brain VEGF inhibition on isoflurane-induced cognitive impairment in an aged rat model of POCD. VEGF protein expression was increased in the hippocampus after isoflurane exposure, suggesting that inhalation anaesthesia induces hippocampal VEGF protein overexpression in aged rats. Pretreatment with 2 mg/kg RB-222, an anti-VEGF neutralizing antibody, may partially abolish the degradation of occludin protein in cerebral capillaries, thereby maintaining the ultrastructural and functional integrity of the hippocampal BBB. Inhibition of VEGF also significantly attenuated the isoflurane-induced cognitive deficits in the Morris water maze task. Together, our findings show, for the first time, that elevated expression of brain VEGF after isoflurane exposure contributes to POCD in aged rats. Therefore, therapeutic strategies involving VEGF should take into consideration its role in the pathogenesis of POCD.