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Isoflurane-Induced Postoperative Neurovascular and Cognitive Dysfunction Is Associated with VEGF Overexpression in Aged Rats

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Abstract

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.

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Funding

This work was supported by grants from the National Natural Science Foundation of China (Nos. 81600933), Shanghai Pudong New District Science and Technology Development Fund Medical and Health Project of China (No. PKJ2018-Y56), and the Hundred Faculty Talent Pool Program at Shanghai University of Medicine & Health Sciences in China.

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YYC and XYG conceived and designed the experiments; YYC, ZQL and NY performed the experiments; YYC and ZQL analysed the data; YYC and XYG wrote the paper. All authors read and approved the final manuscript.

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Correspondence to Xiangyang Guo.

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Our research was performed with the approval of the Peking University Biomedical Ethics Committee Experimental Animal Ethics Branch (Approval No. 20150041).

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All named authors have given consent for publication.

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The authors declare that they have no competing interests.

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Zhengqian Li collaborated on this work; he is co-first author of this article.

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Cao, Y., Li, Z., Ma, L. et al. Isoflurane-Induced Postoperative Neurovascular and Cognitive Dysfunction Is Associated with VEGF Overexpression in Aged Rats. J Mol Neurosci 69, 215–223 (2019). https://doi.org/10.1007/s12031-019-01350-8

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  • DOI: https://doi.org/10.1007/s12031-019-01350-8

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