Electroacupuncture Acutely Improves Cerebral Blood Flow and Attenuates Moderate Ischemic Injury via an Endothelial Mechanism in Mice

Ji Hyun Kim,Hwa Kyoung Shin,Kyung Ha Choi,Byung-Cheul Shin,Sun Sik Bae,Byung Tae Choi,Young Jung Jang,Jens Minnerup

doi:10.1371/journal.pone.0056736

Abstract

Electroacupuncture (EA) is a novel therapy based on traditional acupuncture combined with modern eletrotherapy that is currently being investigated as a treatment for acute ischemic stroke. Here, we studied whether acute EA stimulation improves tissue and functional outcome following experimentally induced cerebral ischemia in mice. We hypothesized that endothelial nitric oxide synthase (eNOS)-mediated perfusion augmentation was related to the beneficial effects of EA by interventions in acute ischemic injury. EA stimulation at Baihui (GV20) and Dazhui (GV14) increased cerebral perfusion in the cerebral cortex, which was suppressed in eNOS KO, but there was no mean arterial blood pressure (MABP) response. The increased perfusion elicited by EA were completely abolished by a muscarinic acetylcholine receptor (mAChR) blocker (atropine), but not a β-adrenergic receptor blocker (propranolol), an α-adrenergic receptor blocker (phentolamine), or a nicotinic acetylcholine receptor (nAChR) blocker (mecamylamine). In addition, EA increased acetylcholine (ACh) release and mAChR M3 expression in the cerebral cortex. Acute EA stimulation after occlusion significantly reduced infarct volume by 34.5% when compared to a control group of mice at 24 h after 60 min-middle cerebral artery occlusion (MCAO) (moderate ischemic injury), but not 90-min MCAO (severe ischemic injury). Furthermore, the impact of EA on moderate ischemic injury was totally abolished in eNOS KO. Consistent with a smaller infarct size, acute EA stimulation led to prominent improvement of neurological function and vestibule-motor function. Our results suggest that acute EA stimulation after moderate focal cerebral ischemia, but not severe ischemia improves tissue and functional recovery and ACh/eNOS-mediated perfusion augmentation might be related to these beneficial effects of EA by interventions in acute ischemic injury.

Highlights

Despite decades of intense research, current treatments for acute stroke are far from optimal
We provide evidence that acute EA stimulation at Baihui (GV20) and Dazhui (GV14) after moderate focal cerebral ischemia improves tissue and functional recovery, and that ACh/endothelial nitric oxide synthase (eNOS)-mediated perfusion augmentation might be related to these beneficial effects of EA in response to interventions in moderate ischemic injury
Our results showed that EA stimulation increased perfusion in the cerebral cortex, which was almost abolished by a muscarinic acetylcholine receptor (mAChR) blocker

Summary

Introduction

Despite decades of intense research, current treatments for acute stroke are far from optimal. Electroacupuncture (EA) is a traditional therapy that has been widely applied for treatment of ischemic stroke because it has been shown to improve its outcome in experimental animals [1,2,3,4,5,6,7,8,9] and clinical practice [10,11,12,13]. The severity of stroke might be a major confounding factor, few animal studies have been conducted to investigate the effect of EA according to the severity of cerebral ischemia. To assess the protective effects of EA against moderate and severe ischemic injury, the mice received 20 min-EA stimulation immediately after 60 min- and 90 min-middle cerebral artery occlusion (MCAO)

Methods

Results

Conclusion