Neural Regeneration Research ›› 2024, Vol. 19 ›› Issue (4): 887-894.doi: 10.4103/1673-5374.382252

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Sustained release of vascular endothelial growth factor A and basic fibroblast growth factor from nanofiber membranes reduces oxygen/glucose deprivation-induced injury to neurovascular units#br#

Yifang Wu1, #, Jun Sun1, #, Qi Lin2, Dapeng Wang1, *, Jian Hai1, *   

  1. 1Department of Neurosurgery, Tongji Hospital, School of Medicine, Tongji University, Shanghai, China; 2Department of Pharmacy, Institute of Medical Sciences, Shanghai Jiao Tong University School of Medicine, Shanghai, China
  • Online:2024-04-15 Published:2023-09-15
  • Contact: Dapeng Wang, MD, wdpboj@126.com; Jian Hai, MD, haijiandoct@zoho.com.cn.
  • Supported by:
    The study was supported by the National Natural Science Foundation of China, Nos. 81974207 (to JH), 82001383 (to DW); and the Special Clinical Research Project of Health Profession of Shanghai Municipal Health Commission, No. 20204Y0076 (to DW).

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Abstract: Upregulation of vascular endothelial growth factor A/basic fibroblast growth factor (VEGFA/bFGF) expression in the penumbra of cerebral ischemia can increase vascular volume, reduce lesion volume, and enhance neural cell proliferation and differentiation, thereby exerting neuroprotective effects. However, the beneficial effects of endogenous VEGFA/bFGF are limited as their expression is only transiently increased. In this study, we generated multilayered nanofiber membranes loaded with VEGFA/bFGF using layer-by-layer self-assembly and electrospinning techniques. We found that a membrane containing 10 layers had an ideal ultrastructure and could efficiently and stably release growth factors for more than 1 month. This 10-layered nanofiber membrane promoted brain microvascular endothelial cell tube formation and proliferation, inhibited neuronal apoptosis, upregulated the expression of tight junction proteins, and improved the viability of various cellular components of neurovascular units under conditions of oxygen/glucose deprivation. Furthermore, this nanofiber membrane decreased the expression of Janus kinase-2/signal transducer and activator of transcription-3 (JAK2/STAT3), Bax/Bcl-2, and cleaved caspase-3. Therefore, this nanofiber membrane exhibits a neuroprotective effect on oxygen/glucose-deprived neurovascular units by inhibiting the JAK2/STAT3 pathway.

Key words: brain ischemia, brain microvascular endothelial cell, nanofiber membrane, neurovascular unit