Early Post-Stroke Electroacupuncture Promotes Motor Function Recovery in Post-Ischemic Rats by Increasing the Blood and Brain Irisin

Early  as defined means they have no clue if spontaneous recovery caused all this recovery they measured instead of the electroacupuncture or irisin.

Early Post-Stroke Electroacupuncture Promotes Motor Function Recovery in Post-Ischemic Rats by Increasing the Blood and Brain Irisin

Authors Liu L, Zhang Q, Li M, Wang N, Li C, Song D, Shen X, Luo L, Fan Y, Xie H, Wu Y

Received 3 November 2020

Accepted for publication 25 January 2021

Published 1 March 2021 Volume 2021:17 Pages 695—702

DOI https://doi.org/10.2147/NDT.S290148

Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 3

Editor who approved publication: Dr Yuping Ning

Li Liu,^1,* Qun Zhang,^1,* Mingyue Li,² Nianhong Wang,¹ Ce Li,¹ Di Song,³ Xueyan Shen,¹ Lu Luo,¹ Yunhui Fan,¹ Hongyu Xie,¹ Yi Wu<sup>1

1</sup>Department of Rehabilitation Medicine, Huashan Hospital, Fudan University, Shanghai, People’s Republic of China; ²Department of Rehabilitation Medicine, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, People’s Republic of China; ³Department of Rehabilitation Medicine, The Affiliated Sixth People’s Hospital of Shanghai Jiaotong University, Shanghai, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Hongyu Xie; Yi Wu
Department of Rehabilitation Medicine, Huashan Hospital, Fudan University, 12 Wulumuqi Middle Road, Shanghai, 200040, People’s Republic of China
Email huangdaitian@163.com; 16111220064@fudan.edu.cn

Objective: Recent studies have shown that irisin, a novel peptide hormone derived from muscles, could be used as a potential therapeutic drug against ischemic stroke. Moreover, electroacupuncture (EA) is widely used in the treatment of ischemic stroke. Yet, whether irisin is involved in the EA neuroprotection remains unclear. The following study investigated the association between serum and peri-lesional cortex irisin and EA-induced post-stroke motor recovery in rats.
Methods: The middle cerebral artery occlusion (MCAO) method was used to induce ischemic stroke in rats. Rats were randomly divided into two groups: a middle cerebral artery occlusion (MCAO) group (MCAO rats without treatment) and an electroacupuncture (EA) group (MCAO rats treated with EA). On the 3rd day post-stroke, infarct volume, behavioral deficits, surviving neurons, irisin protein expression in peri-infarction cortex, muscle tissue, and serum were evaluated to identify the neuroprotective of EA in acute ischemic stroke.
Results: Compared with the MCAO group, the EA group showed better behavioral performance, a smaller cerebral infarct volume, more surviving neurons, and a significant increase in irisin expression in the peri-infarction cortex and serum (p< 0.05). However, no difference in irisin expression in the muscle tissue was found between the MCAO group and the EA group (p> 0.05).
Conclusion: EA promotes motor function recovery, reduces the volume of cerebral infarction, and alleviates neuronal death following ischemic stroke by enhancing the expression of irisin in both the blood and peri-lesional cortex.

Keywords: ischemic stroke, electroacupuncture, irisin

Introduction

Stroke is a leading cause of morbidity and mortality worldwide.¹ Acute thrombolytic therapy is the most effective treatment for patients suffering from ischemic stroke.² This kind of therapy is usually given within 4–6 hours after onset of an ischemic stroke, while its effectiveness beyond this time frame (>6 h) still remains debatable. Ischemic stroke is a complex inflammatory cascade. Cerebral ischemia can cause acute neuroinflammation and neuronal injury. In the subacute and chronic phases, cerebral ischemic inflammation can lead to glial cell proliferation, neuronal apoptosis, and brain tissue atrophy. These processes are associated with the impairment of nerve function.³

Recent studies have shown that irisin, cleaved from precursor fibronectin type III domain-containing protein 5 (FNDC5), could be used as a potential therapeutic drug against ischemic stroke. Emerging evidence has indicated that the serum levels of irisin could predict outcomes of patients with ischemic stroke.⁴ In addition, irisin can also promote neuronal cell survival⁵ and inhibit post-stroke inflammation, reducing cerebral infarction volume in MCAO models.⁶ Since irisin is released from skeletal muscle during exercise,⁷ any treatment that stimulates muscle contraction may be used as a potential therapy to increase the irisin post-stroke. However, it is still unclear whether peripheral or central irisin mediates the effects in the brain.

Previous studies have found that early EA can improve neurobehavioural functional recovery and reduce infarct volume by inhibiting the brain inflammation,⁸ oxidative stress,⁹ and promoting angiogenesis.¹⁰ Moreover, EA stimulation at peripheral limbs, for instance, at Zusanli (ST36) and Quchi (LI11) points, could also increase the serum factors, like brain-derived neurotrophic factor (BDNF) and glial cell line-derived neurotrophic factor (GDNF).¹¹ Recent studies found that long-term EA stimulation promotes the expression of FNDC5 in skeletal muscle of diet-induced obesity rats.¹² However, whether irisin is involved in EA neuroprotection remains unclear.

The aim of this study was to investigate the efficacy of EA stimulation at Zusanli (ST36) and Quchi (LI11) points on post-stroke recovery. In order to further explore the early EA neuroprotection mechanism, we analyzed different irisin concentrations in the muscle, serum, and pei-infarct cortex on the 3rd day of the post-ischemic stroke. We hypothesized that EA stimulates muscle contraction, increasing the skeletal muscle-originated irisin in either blood or the peri-lesional cerebral cortex, thus resulting in an infarct reduction (Figure 1).