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

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.

A systematic review and meta-analysis of Baihui (GV20)-based scalp acupuncture in experimental ischemic stroke

“…By reading the full text of the remaining 208 articles which reported the efficacy of BBA in animal models of focal cerebral ischemia, 54 studies were excluded because the outcome measure was neither neurological function score (NFS) nor infarct volume (IV); 48 studies were excluded because other forms of acupuncture or TCM were used in control group; 34 were excluded because of combination with body acupunctures; 18 studies were removed due to the deficiency of useful data and the problem of duplicate publication. Ultimately, 54 eligible studies were identified (Figure 1)34353637383940414243444546474849505152535455565758596061626364656667686970717273747576777879; Li JA, unpublished Master's thesis, 2005; Wang C, unpublished Master's thesis, 2005; Jin JF, unpublished PhD thesis, 2005; Luo T, unpublished Master's thesis, 2006; Chen X, unpublished Master's thesis, 2007; Ding J, unpublished Master's thesis, 2007; Wang EL, unpublished PhD thesis, 2008; Wu HY, unpublished PhD thesis, 2010.…”

“…The time of ischemia varied from 30 minutes to 3 hours. Chloral hydrate were used in 32 studies (n = 59.2%) to induce anesthesia, isoflurane in 7 studies34353642455771, Pentobarbital in 9 studies383940414344464760, urethane59 and thiopental69 in one study respectively, while no report of anesthetics in the remaining 4 studies66677879.…”

“…The selection of acupoints were as follows: 12 studies used Baihui mono-therapy343536373839404142434445; 12 studies selected Baihui plus Shuigou585960616263; Li JA, unpublished Master's thesis, 2005; Wang C, unpublished Master's thesis, 2005; Jin JF, unpublished PhD thesis, 2005; Luo T, unpublished Master's thesis, 2006; Chen X, unpublished Master's thesis, 2007; Ding J, unpublished Master's thesis, 2007; 12 studies selected Baihui plus Dazhui464748495051525354555657; 7 studies used scalp penetration needling through Baihui to other acupoints64656667686970; the rest of the 11 studies selected Baihui plus other acupoints. Meanwhile, IV was used as the outcome measure in 24 groups (44.4%), and NFS was used in forty-nine groups (90.7%).…”

“…(2) Electroacupuncture (EA) preconditioning at Baihui (GV20) could attenuate brain edema and blood brain barrier (BBB) disruption caused by cerebral ischemia and was mainly through decreasing matrix metalloproteinase (MMP)- 9 expression and activity14. (3) EA at Baihui (GV20) and Dazhui (GV14) could increase cerebral blood flow and improve tissue and function recovery through acetylcholine/endothelial nitric oxide synthase (eNOS)-mediated perfusion augmentation in acute moderate focal cerebral ischemia15. (4) EA pretreatment at Baihui (GV 20) strongly protects the brain against transient cerebral ischemic injury through the anti-inflammatory effects of α7 nicotinic acetylcholine receptors (α7nAChR) activation16.…”

Depletion of the cereblon gene activates the unfolded protein response and protects cells from ER stress-induced cell death

“…Ischemia was induced by occluding the MCA, as described previously [16,17]. Size of the cerebral infarct was determined on 2,3,5-triphenyltetrazolium chloride (TTC)-stained, 2 mm-thick brain section.…”