Related Experiment Video
Updated: Jun 29, 2026
Author Spotlight: Establishing a Reliable Distal MCA Occlusion Model in Mice for Stroke Research
Published on: December 15, 2023
BK Channel-Mediated Microglial Phagocytosis Alleviates Neurological Deficit After Ischemic Stroke
Shuxian Huang1, Tingting Chen1, Qian Suo1
1Shanghai Jiao Tong University Affiliated Sixth People's Hospital, School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China.
Abstract:
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.
Insights
Large-conductance calcium-activated potassium (BK) channels in microglia aid stroke recovery. Activating BK channels improved neurological function and reduced neuronal apoptosis after ischemic stroke by enhancing microglial phagocytosis.
Area of Science:
- Neuroscience
- Cell Biology
- Pharmacology
Background:
- Microglial phagocytosis is crucial for neurological recovery post-stroke.
- Large-conductance calcium-activated potassium (BK) channels are present in activated microglia.
- BK channel deficiency exacerbates ischemic brain injury, but their role in microglial phagocytosis after stroke is unclear.
Purpose of the Study:
- To investigate the role of BK channels in microglial phagocytosis after ischemic stroke.
- To determine if BK channel activation benefits neurological outcomes by modulating microglial phagocytosis.
Main Methods:
- Transient middle cerebral artery occlusion (tMCAO) model in ICR mice.
- Treatment with BK channel activator (NS19504) and inhibitor (Paxilline).
- Assessment of neurological deficits, microglial phagocytosis of fluorescent beads and neuronal debris in primary microglia exposed to oxygen-glucose deprivation (OGD).
Main Results:
- BK channel expression decreased after tMCAO.
- NS19504 treatment alleviated neurological deficits in tMCAO mice.
- NS19504 enhanced microglial phagocytosis and reduced neuronal apoptosis post-OGD, effects reversed by Paxilline.
- NS19504 increased phosphorylated ERK1/2 levels post-stroke.
Conclusions:
- Microglial BK channels play a beneficial role in neurological recovery after ischemic stroke.
- BK channel activation promotes microglial phagocytosis, reducing neuronal damage.
- Microglial BK channels represent a potential therapeutic target for acute ischemic stroke.
Related Concept Videos
01:15Ischemic Stroke l: Introduction
01:15Ischemic Stroke ll: Pathophysiology