Electroacupuncture Activates Neuroplasticity in the Motor Cortex and Corticospinal Tract via the mTOR Pathway in a Rat P-MCAO Model

Abstract

Electroacupuncture (EA) combines traditional Chinese medicine acupuncture theory with modern scientific technology. It is a promising therapy for the treatment of cerebrovascular diseases such as cerebral infarction. A large number of clinical studies have shown that EA promotes recovery of neurological function after cerebral infarction, however, the underlying mechanisms behind its effects remain unclear. We tested whether EA stimulation of the Zusanli (ST36) and Neiguan (PC6) acupoints activates neuroplasticity in rats with ischemic stroke and whether this involves the regulation of axonal regeneration through the mTOR pathway. 24 h after permanent middle cerebral artery occlusion (p-MCAO) in rats, EA treatment was started for 20 min, daily, for 14 days. We found that EA significantly reduced Modified Neurological Severity Scores (mNSS), cerebral infarct volume, and apoptosis of neuronal cells. EA also significantly increased the expression of the neuroplasticity-associated proteins GAP-43 and SYN and upregulated the phosphorylation levels of AKT, mTOR, S6, and PTEN to promote CST axon sprouting in the spinal cord at C1–C4 levels. The positive effects of EA were blocked by the administration of the mTOR inhibitor Rapamycin. In short, we found that EA of the Zusanli (ST36) and Neiguan (PC6) acupoints in p-MCAO rats induced neuroprotective and neuroplastic effects by regulating the mTOR signaling pathway. It promoted neuroplasticity activated by axon regeneration in the contralateral cortex and corticospinal tract. Activation of such endogenous remodeling is conducive to neurological recovery and may help explain the positive clinical effects seen in patients with infarcts.

Trends and hotspots in acupuncture treatment of rat models of stroke: a bibliometric analysis from 2004 to 2023

“…During the early stage of ischemic stroke, cerebral ischemia significantly reduces the supply of nutrients such as glucose and oxygen, leading to inadequate or exhausted energy reserves in nerve cells, culminating in cell edema, necrosis, demyelination, and axonal demyelination ( Yuan et al, 2021 ). Studies have confirmed that electroacupuncture can regulate the mTOR signaling pathway to induce neuroprotection and neuroplasticity, thereby promoting axon regeneration in the contralateral cortex and corticospinal tract, activating neuroplasticity, and achieving the purpose of neurological recovery ( Zheng et al, 2016 ; Chen et al, 2020 ; Zhang S. H. et al, 2022 ; Zhang Y. et al, 2022 ). Neural regeneration, angiogenesis, and synaptic regeneration are crucial for autonomic plasticity in the brain, potentially elucidating the positive clinical effects in patients with cerebral infarction.…”

A bibliometric analysis of acupuncture for cerebral infarction from 1993 to 2023

“…Significant increase in dendritic spine density and inhibition of autophagy in ischemic cortical neurons indicate that electroacupuncture plays a neuroprotective role during the reperfusion period after MCAO in rats. Zhang et al ( 41 ) found that acupuncture at the Zusanli and Neiguan acupoints in p-MCAO rats promoted the neural plasticity of axonal regeneration activation in the contralateral cortex and corticospinal tract of the mTOR signaling pathway, promoting neurological function recovery. The prominent cited author is Si et al ( 42 ).…”

Exploring the mechanisms under Zuogui Pill’s treatment of ischemic stroke through network pharmacology and in vitro experimental verification

“…mTOR, p53, and Wnt signaling pathways are all associated with nerve regeneration and repair after ischemic brain injury. mTOR is a key signal pathway regulating the intrinsic growth ability of neurite outgrowth and axonal regeneration ( Park et al, 2008 ; Bei et al, 2016 ; Liu et al, 2017 ; Zhang et al, 2022 ). The phosphorylation expression level of its downstream protein p-S6 can indirectly characterize the activity of mTOR (( Ma et al, 2021 ; Li et al, 2022 ).…”