Electroacupuncture enhances rehabilitation through miR-181b targeting PirB after ischemic stroke

Abstract

Recent studies have demonstrated microRNAs (miRNAs) and proteins are beneficial to axon regeneration, which may be involved in Electroacupuncture (EA) therapy against stroke. In this study, we aimed to determine the pivotal role of PirB in EA-produced rehabilitation against ischemic stroke; and to screen and investigate the potential miRNAs directly regulating PirB expression. The results showed EA treatment enhanced axon regeneration and new projections from the corticospinal tract at 28 d after cerebral ischemic reperfusion injury of rats. Then, we found EA decreased pirb mRNA and PirB protein expression in the penumbra within 28 days after reperfusion. The reduction of PirB expression facilitated neurite outgrowth after oxygen-glucose deprivation injury. The miRNA microarray showed the level of twenty kinds of miRNAs changed in the penumbra after EA administration. The bioinformatics study and luciferase assay verified miR-181b directly regulated pirb mRNA expression. EA increased miR-181b levels in the penumbras, and improved neurobehavioral function rehabilitation through miR-181b direct targeting of pirb mRNA to regulate the expression of PirB, RhoA and GAP43. In conclusion, we provide the first evidence that EA enhances rehabilitation against stroke by regulating epigenetic changes to directly act on its targets, such as the miR-181b/PirB/RhoA/GAP43 axis, which is a novel mechanism of EA therapy.

Mechanisms Involved in the Neuroprotection of Electroacupuncture Therapy for Ischemic Stroke

“…Hippocampal synaptic plasticity induced by EA was associated with miR-134-mediated LIMK1, involved in the improvement of memory and learning in the period of ischemic-injury recovery (Liu et al, 2017). MiR-181b may be enhanced by EA with 2/10 Hz for 5 successive days in the penumbras, and EA may prompt neurobehavioral function recovery via regulating the expression of RhoA,GAP43, and PirB (Deng et al, 2016).…”

“…Tan et al demonstrate that the up-regulation of NgR1 and Nogo-A induced by ischemia may be reversed by EA treatment at days 14 and 28 following ischemic stroke in renovascular hypertensive rats, and EA may alleviate neural damage following cervical spinal cord injury (Tan et al, 2014a). Deng et al show that PirB protein and pirb mRNA levels in the penumbra are reduced by EA treatment at a dense-disperse frequency of 2/10 Hz and an intensity of 1–2 mA at the Baihui point within 28 days following ischemia/reperfusion, and the decrease of pirB might promote neurite outgrowth following oxygen-glucose deprivation damage (Deng et al, 2016).…”

Applications of Acupuncture Therapy in Modulating the Plasticity of Neurodegenerative Disease and Depression: Do MicroRNA and Neurotrophin BDNF Shed Light on the Underlying Mechanism?

“…Analysing the literature on stroke suggested that miR-219a and miR-134, which are closely related to synaptic plasticity, were downregulated by EA treatment [ 26 , 42 ]. Similarly, EA increased miR-181b levels in the penumbra and improved neurobehavioural function [ 46 ]. miR-494 was downregulated and miR-206 was upregulated in the penumbra [ 45 ].…”

“…Similarly, Deng et al treated acupoint GV20 after ischaemic stroke. EA increased miR-181b levels in the penumbras and improved neurobehavioural function [ 46 ].…”

MicroRNA in ischemic stroke

“…В недавнем исследовании В. Deng и соавт. [35] выявили, что электроакупунктура повышает экскрецию мРНК-181b при ИИ в периферических отделах очага ишемии мозга, что в свою очередь приводит к восстановлению поведенческих функций вследствие прямого воздействия мРНК-181b на парный иммуноглобулиноподобный рецептор B.…”