# Electroacupuncture ameliorates neuroinflammation by inhibiting TRPV4 channel in ischemic stroke

**Authors:** Xueqi Ren, Xinyi Gao, Ziqing Li, Yangyang Ding, Ao Xu, Lixia Du, Yufang Yang, Deheng Wang, Zhifei Wang, Shi Shu

PMC · DOI: 10.1111/cns.14618 · 2024-02-09

## TL;DR

Electroacupuncture at specific points reduces brain injury in stroke by suppressing inflammation and a key ion channel called TRPV4.

## Contribution

This study reveals that electroacupuncture reduces neuroinflammation in stroke by inhibiting TRPV4 and M1 microglia/macrophage polarization.

## Key findings

- Electroacupuncture improved neurological outcomes and reduced infarction in MCAO mice.
- EA suppressed M1 polarization of microglia/macrophages and reduced pro-inflammatory cytokines.
- TRPV4 inhibition with GSK219 produced similar effects to EA, but combining both did not enhance outcomes.

## Abstract

We investigated the potential mechanisms underlying the therapeutic efficacy of electroacupuncture (EA) at the Shuigou (GV26) and Baihui (GV20) acupoints in the treatment of ischemic stroke.

We assessed the therapeutic effects of EA on MCAO mice through behavioral studies and TTC staining. Various techniques, such as RT‐PCR, immunofluorescence, and Western blots, were employed to evaluate the activation and polarization of microglia/macrophages, and changes in the TRPV4 ion channel. We used the TRPV4 antagonist GSK2193874 (GSK219) to verify the involvement of TRPV4 in the therapeutic effects of EA.

EA effectively improved neurological impairments and reduced cerebral infarction volume in MCAO mice. It suppressed activated microglia/macrophages and inhibited their polarization toward the M1 phenotype post‐MCAO. EA also downregulated the expression of pro‐inflammatory cytokines, including Tnf‐α, Il‐6, Il‐1β, and Ccl‐2 mRNA. Furthermore, EA reduced the elevated expression of TRPV4 following MCAO. Treatment with the TRPV4 antagonist GSK219 mirrored the effects of EA in MCAO mice. Notably, the combination of EA and GSK219 did not demonstrate an additive or synergistic effect.

EA may inhibit neuroinflammation and exhibit a protective effect against ischemic brain injury by suppressing TRPV4 and the subsequent M1 polarization of microglia/macrophages.

Electroacupuncture may inhibit neuroinflammation and exhibit a protective effect against ischemic brain injury by suppressing TRPV4 and the subsequent M1 polarization of microglia/macrophages. The Graphical Abstract was created with Figdraw (www.fgdraw.com).

## Linked entities

- **Genes:** TNF (tumor necrosis factor) [NCBI Gene 7124], IL6 (interleukin 6) [NCBI Gene 3569], IL1B (interleukin 1 beta) [NCBI Gene 3553], CCL2 (C-C motif chemokine ligand 2) [NCBI Gene 6347]
- **Proteins:** TRPV4 (transient receptor potential cation channel subfamily V member 4)
- **Chemicals:** GSK2193874 (PubChem CID 53464483)
- **Diseases:** ischemic stroke (MONDO:1060198)
- **Species:** Mus musculus (taxon 10090)

## Full-text entities

- **Genes:** Trpv4 (transient receptor potential cation channel, subfamily V, member 4) [NCBI Gene 63873] {aka 0610033B08Rik, OTRPC4, Trp12, VR-OAC, VRL-2, VROAC}, Ccl2 (C-C motif chemokine ligand 2) [NCBI Gene 20296] {aka HC11, JE, MCAF, MCP-1, MCP1, SMC-CF}, Tnf (tumor necrosis factor) [NCBI Gene 21926] {aka DIF, TNF-a, TNF-alpha, TNFSF2, TNFalpha, Tnfa}, Il6 (interleukin 6) [NCBI Gene 16193] {aka Il-6}, Il1b (interleukin 1 beta) [NCBI Gene 16176] {aka IL-1beta, Il-1b}
- **Diseases:** cerebral infarction (MESH:D002544), ischemic brain injury (MESH:D001930), neuroinflammation (MESH:D000090862), inflammatory (MESH:D007249), neurological impairments (MESH:D009422)
- **Chemicals:** GV20 (-), GSK219 (MESH:C000628859)
- **Species:** Mus musculus (house mouse, species) [taxon 10090]

## Figures

7 figures with captions in the complete paper: https://tomesphere.com/paper/PMC10853892/full.md

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Source: https://tomesphere.com/paper/PMC10853892