High-frequency repetitive transcranial magnetic stimulation promotes neural stem cell proliferation after ischemic stroke
Proliferation of neural stem cells is crucial for promoting neuronal regeneration and repairing cerebral infarction damage. Transcranial magnetic stimulation (TMS) has recently emerged as a tool for inducing endogenous neural stem cell regeneration, but its underlying mechanisms remain unclear. In t...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wolters Kluwer Medknow Publications
2024-01-01
|
| Series: | Neural Regeneration Research |
| Subjects: | |
| Online Access: | http://www.nrronline.org/article.asp?issn=1673-5374;year=2024;volume=19;issue=8;spage=1772;epage=1780;aulast= |
| _version_ | 1797231677768990720 |
|---|---|
| author | Jing Luo Yuan Feng Zhongqiu Hong Mingyu Yin Haiqing Zheng Liying Zhang Xiquan Hu |
| author_facet | Jing Luo Yuan Feng Zhongqiu Hong Mingyu Yin Haiqing Zheng Liying Zhang Xiquan Hu |
| author_sort | Jing Luo |
| collection | DOAJ |
| description | Proliferation of neural stem cells is crucial for promoting neuronal regeneration and repairing cerebral infarction damage. Transcranial magnetic stimulation (TMS) has recently emerged as a tool for inducing endogenous neural stem cell regeneration, but its underlying mechanisms remain unclear. In this study, we found that repetitive TMS effectively promotes the proliferation of oxygen-glucose deprived neural stem cells. Additionally, repetitive TMS reduced the volume of cerebral infarction in a rat model of ischemic stroke caused by middle cerebral artery occlusion, improved rat cognitive function, and promoted the proliferation of neural stem cells in the ischemic penumbra. RNA-sequencing found that repetitive TMS activated the Wnt signaling pathway in the ischemic penumbra of rats with cerebral ischemia. Furthermore, PCR analysis revealed that repetitive TMS promoted AKT phosphorylation, leading to an increase in mRNA levels of cell cycle-related proteins such as Cdk2 and Cdk4. This effect was also associated with activation of the glycogen synthase kinase 3β/β-catenin signaling pathway, which ultimately promotes the proliferation of neural stem cells. Subsequently, we validated the effect of repetitive TMS on AKT phosphorylation. We found that repetitive TMS promoted Ca2+ influx into neural stem cells by activating the P2 calcium channel/calmodulin pathway, thereby promoting AKT phosphorylation and activating the glycogen synthase kinase 3β/β-catenin pathway. These findings indicate that repetitive TMS can promote the proliferation of endogenous neural stem cells through a Ca2+ influx-dependent phosphorylated AKT/glycogen synthase kinase 3β/β-catenin signaling pathway. This study has produced pioneering results on the intrinsic mechanism of repetitive TMS to promote neural function recovery after ischemic stroke. These results provide a strong scientific foundation for the clinical application of repetitive TMS. Moreover, repetitive TMS treatment may not only be an efficient and potential approach to support neurogenesis for further therapeutic applications, but also provide an effective platform for the expansion of neural stem cells. |
| first_indexed | 2024-04-24T15:48:11Z |
| format | Article |
| id | doaj.art-74891c9d1ff54da09c0c2235757cd851 |
| institution | Directory Open Access Journal |
| issn | 1673-5374 |
| language | English |
| last_indexed | 2024-04-24T15:48:11Z |
| publishDate | 2024-01-01 |
| publisher | Wolters Kluwer Medknow Publications |
| record_format | Article |
| series | Neural Regeneration Research |
| spelling | doaj.art-74891c9d1ff54da09c0c2235757cd8512024-04-01T13:06:21ZengWolters Kluwer Medknow PublicationsNeural Regeneration Research1673-53742024-01-011981772178010.4103/1673-5374.389303High-frequency repetitive transcranial magnetic stimulation promotes neural stem cell proliferation after ischemic strokeJing LuoYuan FengZhongqiu HongMingyu YinHaiqing ZhengLiying ZhangXiquan HuProliferation of neural stem cells is crucial for promoting neuronal regeneration and repairing cerebral infarction damage. Transcranial magnetic stimulation (TMS) has recently emerged as a tool for inducing endogenous neural stem cell regeneration, but its underlying mechanisms remain unclear. In this study, we found that repetitive TMS effectively promotes the proliferation of oxygen-glucose deprived neural stem cells. Additionally, repetitive TMS reduced the volume of cerebral infarction in a rat model of ischemic stroke caused by middle cerebral artery occlusion, improved rat cognitive function, and promoted the proliferation of neural stem cells in the ischemic penumbra. RNA-sequencing found that repetitive TMS activated the Wnt signaling pathway in the ischemic penumbra of rats with cerebral ischemia. Furthermore, PCR analysis revealed that repetitive TMS promoted AKT phosphorylation, leading to an increase in mRNA levels of cell cycle-related proteins such as Cdk2 and Cdk4. This effect was also associated with activation of the glycogen synthase kinase 3β/β-catenin signaling pathway, which ultimately promotes the proliferation of neural stem cells. Subsequently, we validated the effect of repetitive TMS on AKT phosphorylation. We found that repetitive TMS promoted Ca2+ influx into neural stem cells by activating the P2 calcium channel/calmodulin pathway, thereby promoting AKT phosphorylation and activating the glycogen synthase kinase 3β/β-catenin pathway. These findings indicate that repetitive TMS can promote the proliferation of endogenous neural stem cells through a Ca2+ influx-dependent phosphorylated AKT/glycogen synthase kinase 3β/β-catenin signaling pathway. This study has produced pioneering results on the intrinsic mechanism of repetitive TMS to promote neural function recovery after ischemic stroke. These results provide a strong scientific foundation for the clinical application of repetitive TMS. Moreover, repetitive TMS treatment may not only be an efficient and potential approach to support neurogenesis for further therapeutic applications, but also provide an effective platform for the expansion of neural stem cells.http://www.nrronline.org/article.asp?issn=1673-5374;year=2024;volume=19;issue=8;spage=1772;epage=1780;aulast=akt/β-catenin signaling; brain stimulation; ca2+ influx; cell proliferation; ischemic stroke; middle cerebral artery occlusion; neural stem cells; neurological rehabilitation; repetitive transcranial magnetic stimulation |
| spellingShingle | Jing Luo Yuan Feng Zhongqiu Hong Mingyu Yin Haiqing Zheng Liying Zhang Xiquan Hu High-frequency repetitive transcranial magnetic stimulation promotes neural stem cell proliferation after ischemic stroke Neural Regeneration Research akt/β-catenin signaling; brain stimulation; ca2+ influx; cell proliferation; ischemic stroke; middle cerebral artery occlusion; neural stem cells; neurological rehabilitation; repetitive transcranial magnetic stimulation |
| title | High-frequency repetitive transcranial magnetic stimulation promotes neural stem cell proliferation after ischemic stroke |
| title_full | High-frequency repetitive transcranial magnetic stimulation promotes neural stem cell proliferation after ischemic stroke |
| title_fullStr | High-frequency repetitive transcranial magnetic stimulation promotes neural stem cell proliferation after ischemic stroke |
| title_full_unstemmed | High-frequency repetitive transcranial magnetic stimulation promotes neural stem cell proliferation after ischemic stroke |
| title_short | High-frequency repetitive transcranial magnetic stimulation promotes neural stem cell proliferation after ischemic stroke |
| title_sort | high frequency repetitive transcranial magnetic stimulation promotes neural stem cell proliferation after ischemic stroke |
| topic | akt/β-catenin signaling; brain stimulation; ca2+ influx; cell proliferation; ischemic stroke; middle cerebral artery occlusion; neural stem cells; neurological rehabilitation; repetitive transcranial magnetic stimulation |
| url | http://www.nrronline.org/article.asp?issn=1673-5374;year=2024;volume=19;issue=8;spage=1772;epage=1780;aulast= |
| work_keys_str_mv | AT jingluo highfrequencyrepetitivetranscranialmagneticstimulationpromotesneuralstemcellproliferationafterischemicstroke AT yuanfeng highfrequencyrepetitivetranscranialmagneticstimulationpromotesneuralstemcellproliferationafterischemicstroke AT zhongqiuhong highfrequencyrepetitivetranscranialmagneticstimulationpromotesneuralstemcellproliferationafterischemicstroke AT mingyuyin highfrequencyrepetitivetranscranialmagneticstimulationpromotesneuralstemcellproliferationafterischemicstroke AT haiqingzheng highfrequencyrepetitivetranscranialmagneticstimulationpromotesneuralstemcellproliferationafterischemicstroke AT liyingzhang highfrequencyrepetitivetranscranialmagneticstimulationpromotesneuralstemcellproliferationafterischemicstroke AT xiquanhu highfrequencyrepetitivetranscranialmagneticstimulationpromotesneuralstemcellproliferationafterischemicstroke |