Manual acupuncture relieves microglia-mediated neuroinflammation in a rat model of traumatic brain injury by inhibiting the RhoA/ROCK2 pathway

Abstract

Objective: To investigate the regulatory mechanism of manual acupuncture (MA) on microglial polarization–mediated neuroinflammation after traumatic brain injury (TBI), focusing on the RhoA/Rho-associated coiled coil-forming protein kinase (ROCK2) pathway. Methods: Sprague Dawley (SD) rats were used to generate a TBI model using Feeney’s freefall epidural impact method. MA was performed on half of the TBI model rats, while the others remained untreated. Acupuncture was administered at GV15, GV16, GV20, GV26, and LI4. At the end of the intervention, rat brain tissue samples were collected, and the microglial M1 polarization status was observed by immunofluorescence labeling of CD86, an M1 microglia-specific protein. RhoA/ROCK2 signaling components were detected by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting. An enzyme-linked immunosorbent assay (ELISA) was used to detect the expression levels of inflammatory factors. Results: Compared with normal rats, the CD86 expression density in the untreated TBI model rats was high and showed an aggregated expression pattern. The genes and proteins of the RhoA/ROCK2 signaling pathway were highly expressed, and inflammatory factors were significantly increased. The CD86 expression density in TBI rats after MA was reduced compared to that in untreated TBI rats and showed a scattered distribution. The expression of RhoA/ROCK2 signaling pathway genes and proteins was also significantly reduced, and inflammatory factors were decreased. Conclusion: These results show that MA may inhibit M1 polarization of microglia by regulating the RhoA/ROCK2 signaling pathway, thereby reducing neuroinflammation in TBI.

Acupuncture promotes nerve repair through the benign regulation of mTOR‐mediated neuronal autophagy in traumatic brain injury rats

“… 17 , 18 , 19 Many studies have demonstrated that acupuncture plays an important role in post‐TBI neural restoration. 20 , 21 , 22 , 23 However, the biological mechanism remains to be clarified. In this work, we revealed neuronal autophagy contributes to the neuroprotective effects of acupuncture.…”

“…Traumatic brain injury (TBI) induced functional brain impairment and neurobehavioral changes are important risk factors for multiple neurodegenerative diseases 17–19 . Many studies have demonstrated that acupuncture plays an important role in post‐TBI neural restoration 20–23 . However, the biological mechanism remains to be clarified.…”

“…It is easy to develop into the second stage if not provided prompt and effective treatment, which causes a poor prognosis and low quality of life (QoL), bringing a huge economic burden to family and society. 4 Many studies 5 , 6 , 7 have proved that acupuncture was beneficial to TBI in brain function restoration and QoL improvement.…”

The Anti-Inflammatory Actions and Mechanisms of Acupuncture from Acupoint to Target Organs via Neuro-Immune Regulation

“…76 Meanwhile, MA at Yamen (GV15), Fengfu (GV16), GV20, Shuigou (GV26), and LI4 enhances brain antioxidant defense, reduces expression of M1 microglia, inhibits RhoA/Rock2 signaling pathway and pro-inflammatory TNF-α, IL-1β, IL-6 in order to abrogate DNA damage of brain tissue near the lesion of traumatic brain injury (TBI) while enhancing neurological function. 77 In the pentylenetetrazole (PTZ)induced epileptic model, MA at GV20 was shown to reduce ROS production, increase SOD and catalase (CAT) activity, inhibit expression of pro-inflammatory factor TNF-α, produce anti-epileptic signal, inhibit abnormal discharge of damaged neurons, and finally reduce the degree of epileptic seizure. 78 When oxygen and ATP energy, required for cell metabolism, are insufficient and the excitotoxicity of glutamate increases, over-activation of the N-methyl-D-aspartate receptor (NMDAR) and, eventually, cell death may result.…”

Editorial: Therapeutic relevance and mechanisms of neuro-immune communication in brain injury

“…The neuroprotective mechanisms of acupuncture for brain injury have been relatively well studied. In the traumatic brain injury model, researchers found that acupuncture inhibits M1 polarization of microglia by regulating RhoA/ROCK2 and TLR4/TRIF/MyD88 signaling pathways, thereby mitigating neuroinflammation in the acute, subacute, and chronic phases after TBI (Cavalli et al, 2018 ; Zhu et al, 2020 ; Cao et al, 2022 ). In stroke, electric acupuncture increases miR-223 and α7nAChR protein levels, inhibits NLRP3 inflammasome activation, and alleviates neuroinflammation (Jiang et al, 2019 ; Sha et al, 2019 ; Xin et al, 2022 ).…”