Journal of Molecular Neuroscience

, Volume 69, Issue 2, pp 215–223 | Cite as

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

  • Yiyun Cao
  • Zhengqian Li
  • Lijun Ma
  • Ning Yang
  • Xiangyang GuoEmail author


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.


Isoflurane Postoperative cognitive dysfunction Vascular endothelial growth factor Blood–brain barrier 


Authors’ Contributions

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.

Funding Information

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.

Compliance with Ethical Standards

Ethics Approval and Consent to Participate

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

Consent for Publication

All named authors have given consent for publication.

Competing Interests

The authors declare that they have no competing interests.


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of AnesthesiologyShanghai Sixth People’s Hospital East Affiliated to Shanghai University of Medicine & Health SciencesShanghaiChina
  2. 2.Department of AnesthesiologyPeking University Third HospitalBeijingChina
  3. 3.Department of Medical ImagingNorth Minzu UniversityYinchuanChina

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