VEGF loaded nanofiber membranes inhibit chronic cerebral hypoperfusion-induced cognitive dysfunction by promoting HIF-1a/VEGF mediated angiogenesis.
VEGF loaded nanofiber membranes inhibit chronic cerebral hypoperfusion-induced cognitive dysfunction by promoting HIF-1a/VEGF mediated angiogenesis.
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DOI：
10.1016/j.nano.2022.102639
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发表时间：
2022-12
期刊：
影响因子：
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通讯作者：
Yifang Wu;Kai-Yan Jin;Dapeng Wang;Qi Lin;Jun Sun;Shao-Hua Su;J. Hai
中科院分区：
文献类型：
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作者：
Yifang Wu;Kai-Yan Jin;Dapeng Wang;Qi Lin;Jun Sun;Shao-Hua Su;J. Hai
我们研究了血管内皮生长因子(VEGF)-纳米纤维膜（NFMs）治疗大鼠慢性脑灌注不足（CCH）模型的潜在作用和机制。VEGF-NFMs治疗促进手术颞叶皮层和海马的血管生成，缓解这两个大脑区域的CBF减少。vegf - nfm的应用改善了NAA/Cr比率的降低，防止了神经元的丢失。VEGF-NFMs粘附可减少手术颞叶皮层tunel阳性细胞的数量，改善受损的突触可塑性，抑制手术颞叶皮层和海马中促炎细胞因子的释放和小胶质细胞和星形胶质细胞的激活。此外，BDNF-TrkB/PI3K/AKT、BDNF-TrkB/ERK和HIF-1a/VEGF/ERK通路参与了VEGF- nfms对cch诱导的神经元损伤的治疗。这些结果表明，vegf - nfm粘附的神经保护作用可能从修复神经血管开始，进而抑制神经元凋亡和神经元及突触损伤，最终抑制认知功能障碍，为vegf - nfm进一步临床转化提供理论基础。
We investigated the potential effects and mechanisms of vascular endothelial growth factor (VEGF)-nanofiber membranes (NFMs) treatment in a rat model of chronic cerebral hypoperfusion (CCH). VEGF-NFMs treatment promoted angiogenesis in surgical temporal cortex and hippocampus, alleviating decreased CBF in these two cerebral regions. VEGF-NFMs application improved reduced NAA/Cr ratio, preventing neuronal loss. VEGF-NFMs sticking decreased the number of TUNEL-positive cells in surgical temporal cortex, ameliorated impaired synaptic plasticity, and inhibited the release of pro-inflammatory cytokines and the activation of microglia and astrocytes in surgical temporal cortex and hippocampus. Furthermore, BDNF-TrkB/PI3K/AKT, BDNF-TrkB/ERK and HIF-1a/VEGF/ERK pathways were involved in the treatment of VEGF-NFMs against CCH-induced neuronal injury. These results showed the neuroprotective effects of VEGF-NFMs sticking may initiate from neurovascular repairing followed by inhibition of neuronal apoptosis and neuronal and synaptic damage, eventually leading to the suppression of cognitive dysfunction, which provided theoretical foundation for further clinical transformation of VEGF-NFMs.