Neuroprotective Effects of VEGF-A Nanofiber Membrane and FAAH Inhibitor URB597 Against Oxygen–Glucose Deprivation-Induced Ischemic Neuronal Injury
Da-Peng Wang,1 Kai-Yan Jin,1 Peng Zhao,2 Qi Lin,3 Kai Kang,4 Jian Hai1 1Department of Neurosurgery, Tong Ji Hospital, Tong Ji University School of Medicine, Shanghai, 200065, People’s Republic of China; 2Institute for Translational Medicine, Institute for Biomedical Engineering and Nanosci...
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Dove Medical Press
2021-05-01
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| Series: | International Journal of Nanomedicine |
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| Online Access: | https://www.dovepress.com/neuroprotective-effects-of-vegf-a-nanofiber-membrane-and-faah-inhibito-peer-reviewed-fulltext-article-IJN |
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| author | Wang DP Jin KY Zhao P Lin Q Kang K Hai J |
| author_facet | Wang DP Jin KY Zhao P Lin Q Kang K Hai J |
| author_sort | Wang DP |
| collection | DOAJ |
| description | Da-Peng Wang,1 Kai-Yan Jin,1 Peng Zhao,2 Qi Lin,3 Kai Kang,4 Jian Hai1 1Department of Neurosurgery, Tong Ji Hospital, Tong Ji University School of Medicine, Shanghai, 200065, People’s Republic of China; 2Institute for Translational Medicine, Institute for Biomedical Engineering and Nanoscience, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, 200092, People’s Republic of China; 3Department of Pharmacy, Institutes of Medical Sciences, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, People’s Republic of China; 4Department of Research and Surveillance Evaluation, Shanghai Center for Health Promotion, Shanghai, 200040, People’s Republic of ChinaCorrespondence: Da-Peng Wang; Jian HaiDepartment of Neurosurgery, Tong Ji Hospital, Tong Ji University School of Medicine, No. 389, Xincun Road, Putuo District, Shanghai, 200065, People’s Republic of ChinaFax +86-21-66111093Email wdpboj@126.com; haijiandoct@zoho.com.cnIntroduction: Brain ischemia is a common neurological disorder worldwide that activates a cascade of pathophysiological events involving decreases in oxygen and glucose levels. Despite substantial efforts to explore its pathogenesis, the management of ischemic neuronal injury remains an enormous challenge. Accumulating evidence suggests that VEGF modified nanofiber (NF) materials and the fatty-acid amide hydrolase (FAAH) inhibitor URB597 exert an influence on alleviating ischemic brain damage. We aimed to further investigate their effects on primary hippocampal neurons, as well as the underlying mechanisms following oxygen–glucose deprivation (OGD).Methods: Different layers of VEGF-A loaded polycaprolactone (PCL) nanofibrous membranes were first synthesized by using layer-by-layer (LBL) self-assembly of electrospinning methods. The physicochemical and biological properties of VEGF-A NF membranes, and their morphology, hydrophilicity, and controlled-release of VEGF-A were then estimated. Furthermore, the effects of VEGF-A NF and URB597 on OGD-induced mitochondrial oxidative stress, inflammatory responses, neuronal apoptosis, and endocannabinoid signaling components were assessed.Results: The VEGF-A NF membrane and URB597 can not only promote hippocampal neuron adhesion and viability following OGD but also exhibited antioxidant/anti-inflammatory and mitochondrial membrane potential protection. The VEGF-A NF membrane and URB597 also inhibited OGD-induced cellular apoptosis through activating CB1R signaling. These results indicate that VEGF-A could be controlled-released by LBL self-assembled NF membranes.Discussion: The VEGF-A NF membrane and URB597 displayed positive synergistic neuroprotective effects through the inhibition of mitochondrial oxidative stress and activation of CB1R/PI3K/AKT/BDNF signaling, suggesting that a VEGF-A loaded NF membrane and the FAAH inhibitor URB597 could be of therapeutic value in ischemic cerebrovascular diseases.Keywords: brain ischemia, cannabinoid receptor, fatty-acid amide hydrolase, mitochondrial oxidative stress, nanofiber, VEGF-A |
| first_indexed | 2024-12-13T16:49:24Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 1178-2013 |
| language | English |
| last_indexed | 2024-12-13T16:49:24Z |
| publishDate | 2021-05-01 |
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| series | International Journal of Nanomedicine |
| spelling | doaj.art-1248ff880b95480899eec87ccb3e0b082022-12-21T23:38:04ZengDove Medical PressInternational Journal of Nanomedicine1178-20132021-05-01Volume 163661367865256Neuroprotective Effects of VEGF-A Nanofiber Membrane and FAAH Inhibitor URB597 Against Oxygen–Glucose Deprivation-Induced Ischemic Neuronal InjuryWang DPJin KYZhao PLin QKang KHai JDa-Peng Wang,1 Kai-Yan Jin,1 Peng Zhao,2 Qi Lin,3 Kai Kang,4 Jian Hai1 1Department of Neurosurgery, Tong Ji Hospital, Tong Ji University School of Medicine, Shanghai, 200065, People’s Republic of China; 2Institute for Translational Medicine, Institute for Biomedical Engineering and Nanoscience, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, 200092, People’s Republic of China; 3Department of Pharmacy, Institutes of Medical Sciences, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, People’s Republic of China; 4Department of Research and Surveillance Evaluation, Shanghai Center for Health Promotion, Shanghai, 200040, People’s Republic of ChinaCorrespondence: Da-Peng Wang; Jian HaiDepartment of Neurosurgery, Tong Ji Hospital, Tong Ji University School of Medicine, No. 389, Xincun Road, Putuo District, Shanghai, 200065, People’s Republic of ChinaFax +86-21-66111093Email wdpboj@126.com; haijiandoct@zoho.com.cnIntroduction: Brain ischemia is a common neurological disorder worldwide that activates a cascade of pathophysiological events involving decreases in oxygen and glucose levels. Despite substantial efforts to explore its pathogenesis, the management of ischemic neuronal injury remains an enormous challenge. Accumulating evidence suggests that VEGF modified nanofiber (NF) materials and the fatty-acid amide hydrolase (FAAH) inhibitor URB597 exert an influence on alleviating ischemic brain damage. We aimed to further investigate their effects on primary hippocampal neurons, as well as the underlying mechanisms following oxygen–glucose deprivation (OGD).Methods: Different layers of VEGF-A loaded polycaprolactone (PCL) nanofibrous membranes were first synthesized by using layer-by-layer (LBL) self-assembly of electrospinning methods. The physicochemical and biological properties of VEGF-A NF membranes, and their morphology, hydrophilicity, and controlled-release of VEGF-A were then estimated. Furthermore, the effects of VEGF-A NF and URB597 on OGD-induced mitochondrial oxidative stress, inflammatory responses, neuronal apoptosis, and endocannabinoid signaling components were assessed.Results: The VEGF-A NF membrane and URB597 can not only promote hippocampal neuron adhesion and viability following OGD but also exhibited antioxidant/anti-inflammatory and mitochondrial membrane potential protection. The VEGF-A NF membrane and URB597 also inhibited OGD-induced cellular apoptosis through activating CB1R signaling. These results indicate that VEGF-A could be controlled-released by LBL self-assembled NF membranes.Discussion: The VEGF-A NF membrane and URB597 displayed positive synergistic neuroprotective effects through the inhibition of mitochondrial oxidative stress and activation of CB1R/PI3K/AKT/BDNF signaling, suggesting that a VEGF-A loaded NF membrane and the FAAH inhibitor URB597 could be of therapeutic value in ischemic cerebrovascular diseases.Keywords: brain ischemia, cannabinoid receptor, fatty-acid amide hydrolase, mitochondrial oxidative stress, nanofiber, VEGF-Ahttps://www.dovepress.com/neuroprotective-effects-of-vegf-a-nanofiber-membrane-and-faah-inhibito-peer-reviewed-fulltext-article-IJNbrain ischemiacannabinoid receptorfatty-acid amide hydrolasemitochondrial oxidative stressnanofibervegf-a |
| spellingShingle | Wang DP Jin KY Zhao P Lin Q Kang K Hai J Neuroprotective Effects of VEGF-A Nanofiber Membrane and FAAH Inhibitor URB597 Against Oxygen–Glucose Deprivation-Induced Ischemic Neuronal Injury International Journal of Nanomedicine brain ischemia cannabinoid receptor fatty-acid amide hydrolase mitochondrial oxidative stress nanofiber vegf-a |
| title | Neuroprotective Effects of VEGF-A Nanofiber Membrane and FAAH Inhibitor URB597 Against Oxygen–Glucose Deprivation-Induced Ischemic Neuronal Injury |
| title_full | Neuroprotective Effects of VEGF-A Nanofiber Membrane and FAAH Inhibitor URB597 Against Oxygen–Glucose Deprivation-Induced Ischemic Neuronal Injury |
| title_fullStr | Neuroprotective Effects of VEGF-A Nanofiber Membrane and FAAH Inhibitor URB597 Against Oxygen–Glucose Deprivation-Induced Ischemic Neuronal Injury |
| title_full_unstemmed | Neuroprotective Effects of VEGF-A Nanofiber Membrane and FAAH Inhibitor URB597 Against Oxygen–Glucose Deprivation-Induced Ischemic Neuronal Injury |
| title_short | Neuroprotective Effects of VEGF-A Nanofiber Membrane and FAAH Inhibitor URB597 Against Oxygen–Glucose Deprivation-Induced Ischemic Neuronal Injury |
| title_sort | neuroprotective effects of vegf a nanofiber membrane and faah inhibitor urb597 against oxygen ndash glucose deprivation induced ischemic neuronal injury |
| topic | brain ischemia cannabinoid receptor fatty-acid amide hydrolase mitochondrial oxidative stress nanofiber vegf-a |
| url | https://www.dovepress.com/neuroprotective-effects-of-vegf-a-nanofiber-membrane-and-faah-inhibito-peer-reviewed-fulltext-article-IJN |
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