Metformin promotes angiogenesis and functional recovery in aged mice after spinal cord injury by adenosine monophosphate-activated protein kinase/endothelial nitric oxide synthase pathway
Treatment with metformin can lead to the recovery of pleiotropic biological activities after spinal cord injury. However, its effect on spinal cord injury in aged mice remains unclear. Considering the essential role of angiogenesis during the regeneration process, we hypothesized that metformin acti...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wolters Kluwer Medknow Publications
2023-01-01
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| Series: | Neural Regeneration Research |
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| Online Access: | http://www.nrronline.org/article.asp?issn=1673-5374;year=2023;volume=18;issue=7;spage=1553;epage=1562;aulast=Zhao |
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| author | Jin-Yun Zhao Xiao-Long Sheng Cheng-Jun Li Tian Qin Run-Dong He Guo-Yu Dai Yong Cao Hong-Bin Lu Chun-Yue Duan Jian-Zhong Hu |
| author_facet | Jin-Yun Zhao Xiao-Long Sheng Cheng-Jun Li Tian Qin Run-Dong He Guo-Yu Dai Yong Cao Hong-Bin Lu Chun-Yue Duan Jian-Zhong Hu |
| author_sort | Jin-Yun Zhao |
| collection | DOAJ |
| description | Treatment with metformin can lead to the recovery of pleiotropic biological activities after spinal cord injury. However, its effect on spinal cord injury in aged mice remains unclear. Considering the essential role of angiogenesis during the regeneration process, we hypothesized that metformin activates the adenosine monophosphate-activated protein kinase/endothelial nitric oxide synthase pathway in endothelial cells, thereby promoting microvascular regeneration in aged mice after spinal cord injury. In this study, we established young and aged mouse models of contusive spinal cord injury using a modified Allen method. We found that aging hindered the recovery of neurological function and the formation of blood vessels in the spinal cord. Treatment with metformin promoted spinal cord microvascular endothelial cell migration and blood vessel formation in vitro. Furthermore, intraperitoneal injection of metformin in an in vivo model promoted endothelial cell proliferation and increased the density of new blood vessels in the spinal cord, thereby improving neurological function. The role of metformin was reversed by compound C, an adenosine monophosphate-activated protein kinase inhibitor, both in vivo and in vitro, suggesting that the adenosine monophosphate-activated protein kinase/endothelial nitric oxide synthase pathway likely regulates metformin-mediated angiogenesis after spinal cord injury. These findings suggest that metformin promotes vascular regeneration in the injured spinal cord by activating the adenosine monophosphate-activated protein kinase/endothelial nitric oxide synthase pathway, thereby improving the neurological function of aged mice after spinal cord injury. |
| first_indexed | 2024-04-10T23:23:43Z |
| format | Article |
| id | doaj.art-fe5f7ba85664418c92a45648ce18dd01 |
| institution | Directory Open Access Journal |
| issn | 1673-5374 |
| language | English |
| last_indexed | 2024-04-10T23:23:43Z |
| publishDate | 2023-01-01 |
| publisher | Wolters Kluwer Medknow Publications |
| record_format | Article |
| series | Neural Regeneration Research |
| spelling | doaj.art-fe5f7ba85664418c92a45648ce18dd012023-01-12T13:29:30ZengWolters Kluwer Medknow PublicationsNeural Regeneration Research1673-53742023-01-011871553156210.4103/1673-5374.360245Metformin promotes angiogenesis and functional recovery in aged mice after spinal cord injury by adenosine monophosphate-activated protein kinase/endothelial nitric oxide synthase pathwayJin-Yun ZhaoXiao-Long ShengCheng-Jun LiTian QinRun-Dong HeGuo-Yu DaiYong CaoHong-Bin LuChun-Yue DuanJian-Zhong HuTreatment with metformin can lead to the recovery of pleiotropic biological activities after spinal cord injury. However, its effect on spinal cord injury in aged mice remains unclear. Considering the essential role of angiogenesis during the regeneration process, we hypothesized that metformin activates the adenosine monophosphate-activated protein kinase/endothelial nitric oxide synthase pathway in endothelial cells, thereby promoting microvascular regeneration in aged mice after spinal cord injury. In this study, we established young and aged mouse models of contusive spinal cord injury using a modified Allen method. We found that aging hindered the recovery of neurological function and the formation of blood vessels in the spinal cord. Treatment with metformin promoted spinal cord microvascular endothelial cell migration and blood vessel formation in vitro. Furthermore, intraperitoneal injection of metformin in an in vivo model promoted endothelial cell proliferation and increased the density of new blood vessels in the spinal cord, thereby improving neurological function. The role of metformin was reversed by compound C, an adenosine monophosphate-activated protein kinase inhibitor, both in vivo and in vitro, suggesting that the adenosine monophosphate-activated protein kinase/endothelial nitric oxide synthase pathway likely regulates metformin-mediated angiogenesis after spinal cord injury. These findings suggest that metformin promotes vascular regeneration in the injured spinal cord by activating the adenosine monophosphate-activated protein kinase/endothelial nitric oxide synthase pathway, thereby improving the neurological function of aged mice after spinal cord injury.http://www.nrronline.org/article.asp?issn=1673-5374;year=2023;volume=18;issue=7;spage=1553;epage=1562;aulast=Zhaoadenosine monophosphate-activated protein kinase/endothelial nitric oxide synthase pathway; angiogenesis; aged mice; compound c; metformin; spinal cord injury |
| spellingShingle | Jin-Yun Zhao Xiao-Long Sheng Cheng-Jun Li Tian Qin Run-Dong He Guo-Yu Dai Yong Cao Hong-Bin Lu Chun-Yue Duan Jian-Zhong Hu Metformin promotes angiogenesis and functional recovery in aged mice after spinal cord injury by adenosine monophosphate-activated protein kinase/endothelial nitric oxide synthase pathway Neural Regeneration Research adenosine monophosphate-activated protein kinase/endothelial nitric oxide synthase pathway; angiogenesis; aged mice; compound c; metformin; spinal cord injury |
| title | Metformin promotes angiogenesis and functional recovery in aged mice after spinal cord injury by adenosine monophosphate-activated protein kinase/endothelial nitric oxide synthase pathway |
| title_full | Metformin promotes angiogenesis and functional recovery in aged mice after spinal cord injury by adenosine monophosphate-activated protein kinase/endothelial nitric oxide synthase pathway |
| title_fullStr | Metformin promotes angiogenesis and functional recovery in aged mice after spinal cord injury by adenosine monophosphate-activated protein kinase/endothelial nitric oxide synthase pathway |
| title_full_unstemmed | Metformin promotes angiogenesis and functional recovery in aged mice after spinal cord injury by adenosine monophosphate-activated protein kinase/endothelial nitric oxide synthase pathway |
| title_short | Metformin promotes angiogenesis and functional recovery in aged mice after spinal cord injury by adenosine monophosphate-activated protein kinase/endothelial nitric oxide synthase pathway |
| title_sort | metformin promotes angiogenesis and functional recovery in aged mice after spinal cord injury by adenosine monophosphate activated protein kinase endothelial nitric oxide synthase pathway |
| topic | adenosine monophosphate-activated protein kinase/endothelial nitric oxide synthase pathway; angiogenesis; aged mice; compound c; metformin; spinal cord injury |
| url | http://www.nrronline.org/article.asp?issn=1673-5374;year=2023;volume=18;issue=7;spage=1553;epage=1562;aulast=Zhao |
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