Combined VEGF and bFGF loaded nanofiber membrane protects against neuronal injury and hypomyelination in a rat model of chronic cerebral hypoperfusion.
Combined VEGF and bFGF loaded nanofiber membrane protects against neuronal injury and hypomyelination in a rat model of chronic cerebral hypoperfusion.
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DOI：
10.1016/j.intimp.2023.111108
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发表时间：
2023-10
影响因子：
5.6
通讯作者：
Yifang Wu;Jun Sun;Ming Chen;Qi Lin;Kai-Yan Jin;Shao-Hua Su;J. Hai
中科院分区：
文献类型：
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作者：
Yifang Wu;Jun Sun;Ming Chen;Qi Lin;Kai-Yan Jin;Shao-Hua Su;J. Hai
慢性脑低灌流(CCH)所致的脑缺血损伤目前尚无有效的治疗靶点。血管内皮生长因子(VEGF)和碱性成纤维细胞生长因子(BFGF)被发现是神经和血管生成的诱导剂。我们先前制作了一种纳米纤维膜(NFM)，使VEGF和bFGF的长期释放长达35天，这可能使VEGF和bFGFNFM成为潜在的脑缺血保护剂。本研究通过大鼠脑出血模型，观察脑复康对脑组织中血管内皮生长因子和碱性成纤维细胞生长因子的影响，并探讨其作用机制。应用血管内皮生长因子+碱性成纤维细胞生长因子NFM可增加紧密连接蛋白的表达，维持血脑屏障的完整性，减轻血管源性脑水肿。此外，血管内皮细胞生长因子+碱性成纤维细胞生长因子NFM贴剂可促进血管生成，增加脑血流量。此外，血管内皮生长因子+碱性成纤维细胞生长因子NFM治疗可抑制神经元的凋亡，减少神经元的丢失。此外，VEGF1+bFGFNFM可抑制小胶质细胞的活化，并阻断NLRP3/Caspase-1/IL-1β通路的启动。此外，给予血管内皮生长因子+碱性成纤维细胞生长因子NFM可阻止突触前/后膜的破坏和髓鞘的丢失，从而减轻突触损伤和脱髓鞘。血管内皮生长因子1+碱性成纤维细胞生长因子NFM对CCH诱导的神经元损伤和髓鞘减少的治疗作用涉及少突胶质细胞发生、神经发生和PI3K/AKT/mTOR通路。这些结果支持了血管内皮生长因子+碱性成纤维细胞生长因子NFM的应用构成了治疗CCH的神经保护策略，作为一种新的神经保护方法，可能值得进一步的临床转化研究，有利于间接手术血管重建。
Currently, there are no effective therapeutic targets for the treatment of chronic cerebral hypoperfusion(CCH)-induced cerebral ischemic injury. Vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) are discovered as the inducers of neurogenesis and angiogenesis. We previously made a nanofiber membrane (NFM), maintaining a long-term release of VEGF and bFGF up to 35 days, which might make VEGF and bFGF NFM as the potential protective agents against cerebral ischemic insult. In this study, the effects of VEGF and bFGF delivered by NFM into brain were investigated as well as their underlying mechanismsin a rat model of CCH. VEGF + bFGF NFM application increased the expressions of tight junction proteins, maintained BBB integrity, and alleviated vasogenic cerebral edema. Furthermore, VEGF + bFGF NFM sticking enhanced angiogenesis and elevated CBF. Besides, VEGF + bFGF NFM treatment inhibited neuronal apoptosis and decreased neuronal loss. Moreover, roofing of VEGF + bFGF NFM attenuated microglial activation and blocked the launch of NLRP3/caspase-1/IL-1β pathway. In addition, VEGF + bFGF NFM administration prevented disruption to the pre/postsynaptic membranes and loss of myelin sheath, relieving synaptic injury and demyelination. Oligodendrogenesis, neurogenesis and PI3K/AKT/mTOR pathway were involved in the treatment of VEGF + bFGF NFM against CCH-induced neuronal injury and hypomyelination. These findings supported that VEGF + bFGF NFM application constitutes a neuroprotective strategy for the treatment of CCH, which may be worth further clinical translational research as a novel neuroprotective approach, benifiting indirect surgical revascularization.