BK Channel-Mediated Microglial Phagocytosis Alleviates Neurological Deficit After Ischemic Stroke
Microglial phagocytosis benefits neurological recovery after stroke. Large-conductance Ca2+-activated K+ currents are expressed in activated microglia, and BK channel knockout aggravates cerebral ischemic injury. However, the effect of BK channels on microglial phagocytosis after ischemic stroke rem...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-07-01
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| Series: | Frontiers in Cellular Neuroscience |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fncel.2021.683769/full |
| _version_ | 1818887744129073152 |
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| author | Shuxian Huang Tingting Chen Qian Suo Rubing Shi Haroon Khan Yuanyuan Ma Yuanyuan Ma Yaohui Tang Guo-Yuan Yang Guo-Yuan Yang Zhijun Zhang |
| author_facet | Shuxian Huang Tingting Chen Qian Suo Rubing Shi Haroon Khan Yuanyuan Ma Yuanyuan Ma Yaohui Tang Guo-Yuan Yang Guo-Yuan Yang Zhijun Zhang |
| author_sort | Shuxian Huang |
| collection | DOAJ |
| description | Microglial phagocytosis benefits neurological recovery after stroke. Large-conductance Ca2+-activated K+ currents are expressed in activated microglia, and BK channel knockout aggravates cerebral ischemic injury. However, the effect of BK channels on microglial phagocytosis after ischemic stroke remains unknown. Here, we explored whether BK channel activation is beneficial for neurological outcomes through microglial phagocytosis after ischemic stroke. ICR mice after transient middle cerebral artery occlusion (tMCAO) were treated with dimethyl sulfoxide (DMSO), BK channel activator NS19504, and inhibitor Paxilline. The results showed a decrease in BK channel expression after tMCAO. BK channel activator NS19504 alleviates neurological deficit after experimental modeling of tMCAO in mice compared to the control. Furthermore, we treated primary microglia with DMSO, NS19504, and Paxilline after oxygen glucose deprivation (OGD). NS19504 promoted primary microglial phagocytosing fluorescent beads and neuronal debris, which reduced neuronal apoptosis after stroke. These effects could be reversed by BK channel inhibitor Paxilline. Finally, NS19504 increased relative phosphorylated extracellular signal-regulated kinase 1/2 expression compared to the Paxilline group at the third day after stroke. Our findings indicate that microglial BK channels are a potential target for acute stage of ischemic stroke therapy. |
| first_indexed | 2024-12-19T16:42:05Z |
| format | Article |
| id | doaj.art-2df97ca70eb1450bbdb3bbac52947acc |
| institution | Directory Open Access Journal |
| issn | 1662-5102 |
| language | English |
| last_indexed | 2024-12-19T16:42:05Z |
| publishDate | 2021-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cellular Neuroscience |
| spelling | doaj.art-2df97ca70eb1450bbdb3bbac52947acc2022-12-21T20:13:45ZengFrontiers Media S.A.Frontiers in Cellular Neuroscience1662-51022021-07-011510.3389/fncel.2021.683769683769BK Channel-Mediated Microglial Phagocytosis Alleviates Neurological Deficit After Ischemic StrokeShuxian Huang0Tingting Chen1Qian Suo2Rubing Shi3Haroon Khan4Yuanyuan Ma5Yuanyuan Ma6Yaohui Tang7Guo-Yuan Yang8Guo-Yuan Yang9Zhijun Zhang10Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, ChinaShanghai Jiao Tong University Affiliated Sixth People’s Hospital, School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, ChinaShanghai Jiao Tong University Affiliated Sixth People’s Hospital, School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, ChinaShanghai Jiao Tong University Affiliated Sixth People’s Hospital, School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, ChinaShanghai Jiao Tong University Affiliated Sixth People’s Hospital, School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, ChinaShanghai Jiao Tong University Affiliated Sixth People’s Hospital, School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, ChinaDepartment of Neurology, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, ChinaShanghai Jiao Tong University Affiliated Sixth People’s Hospital, School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, ChinaShanghai Jiao Tong University Affiliated Sixth People’s Hospital, School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, ChinaDepartment of Neurology, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, ChinaShanghai Jiao Tong University Affiliated Sixth People’s Hospital, School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, ChinaMicroglial phagocytosis benefits neurological recovery after stroke. Large-conductance Ca2+-activated K+ currents are expressed in activated microglia, and BK channel knockout aggravates cerebral ischemic injury. However, the effect of BK channels on microglial phagocytosis after ischemic stroke remains unknown. Here, we explored whether BK channel activation is beneficial for neurological outcomes through microglial phagocytosis after ischemic stroke. ICR mice after transient middle cerebral artery occlusion (tMCAO) were treated with dimethyl sulfoxide (DMSO), BK channel activator NS19504, and inhibitor Paxilline. The results showed a decrease in BK channel expression after tMCAO. BK channel activator NS19504 alleviates neurological deficit after experimental modeling of tMCAO in mice compared to the control. Furthermore, we treated primary microglia with DMSO, NS19504, and Paxilline after oxygen glucose deprivation (OGD). NS19504 promoted primary microglial phagocytosing fluorescent beads and neuronal debris, which reduced neuronal apoptosis after stroke. These effects could be reversed by BK channel inhibitor Paxilline. Finally, NS19504 increased relative phosphorylated extracellular signal-regulated kinase 1/2 expression compared to the Paxilline group at the third day after stroke. Our findings indicate that microglial BK channels are a potential target for acute stage of ischemic stroke therapy.https://www.frontiersin.org/articles/10.3389/fncel.2021.683769/fullischemic strokeBK channelsmicrogliaphagocytosisERK |
| spellingShingle | Shuxian Huang Tingting Chen Qian Suo Rubing Shi Haroon Khan Yuanyuan Ma Yuanyuan Ma Yaohui Tang Guo-Yuan Yang Guo-Yuan Yang Zhijun Zhang BK Channel-Mediated Microglial Phagocytosis Alleviates Neurological Deficit After Ischemic Stroke Frontiers in Cellular Neuroscience ischemic stroke BK channels microglia phagocytosis ERK |
| title | BK Channel-Mediated Microglial Phagocytosis Alleviates Neurological Deficit After Ischemic Stroke |
| title_full | BK Channel-Mediated Microglial Phagocytosis Alleviates Neurological Deficit After Ischemic Stroke |
| title_fullStr | BK Channel-Mediated Microglial Phagocytosis Alleviates Neurological Deficit After Ischemic Stroke |
| title_full_unstemmed | BK Channel-Mediated Microglial Phagocytosis Alleviates Neurological Deficit After Ischemic Stroke |
| title_short | BK Channel-Mediated Microglial Phagocytosis Alleviates Neurological Deficit After Ischemic Stroke |
| title_sort | bk channel mediated microglial phagocytosis alleviates neurological deficit after ischemic stroke |
| topic | ischemic stroke BK channels microglia phagocytosis ERK |
| url | https://www.frontiersin.org/articles/10.3389/fncel.2021.683769/full |
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