Electroacupuncture Pretreatment as a Novel Avenue to Protect Brain against Ischemia and Reperfusion Injury

Table 1

Summary of animals experiments on EA pretreatment.

Reference	Species	EA pretreatment		Models	Infarct reduction	Mechanisms
		ESP	Acupoint
Xiong et al., 2003 [10]	Rats	15 Hz, 1 mA, 30 min/d, 5 d	Baihui (GV20)	2 h MCAO,	~83%, versus control group ~77%, versus isoflurane group	Didnot clarify
Jiang et al., 2004 [33]	Neonatal rats	2/60 Hz, 0.1–0.6-1 mA (10 min each), 30 min	Bilateral Hegu (LI4)	Left pCCAO, 2 h hypoxia	No morphological study	EA pretreatment inhibits the proapoptotic gene via activating KATP
Wang et al., 2005 [11]	Rats	15 Hz, 1 mA, 30 min	Baihui (GV20)	2hMCAO	~55%, EA 2 h before MCAO No protection, EA 0.5, 1, 3 h before MCAO	Rapid ischemic tolerance occurs in 2 h after EA pretreatment, A1R antagonist reverses the neuroprotection
Gao et al., 2006 [34, 35]	Rats	20 Hz, 5 mA, 30 min/d, 3 d	Bilateral Neiguan (PC6)	30 min LADCA ligation, 15 min reperfusion	~47%	Propranolol, antagonist of β-AR abolish the cardioprotective effect
Gao et al., 2007 [36]	Rats	20 Hz, 5 mA, 30 min/d, 3 d	Bilateral Neiguan (PC6)	30 min LADCA ligation, 15 min reperfusion	~45%	β-AR -Gs-protein-cAMP pathway is involved
Xiong et al., 2007 [37]	Rats	2/15 Hz, 1 mA, 30 min/d, 5 d	Baihui (GV20)	2 h MCAO	~67%	EA pretreatment stimulates the release of enkephalins which bind to 𝛿- and 𝜇-opioid receptors to induce the neuroprotection
Gao et al., 2008 [38]	Rats	20 Hz, 5 mA, 30 min/d, 3 d	Bilateral Neiguan (PC6)	Isolated heart,SGIR	No morphological study	AC, PKA, and the L-type Ca^2+channel are involved in the mediation of the antiarrhythmic effect of EA pretreatment
Meng et al., 2008 [39]	Rats	1.7 Hz, 1 mA, 20 min/d, 10 d	Baihui (GV 20), Shenshu (BL 23) Zusanli (ST 36)	1.5 h MCAO	No morphological study	EA pretreatment suppresses the increase of Glu content, downregulates NMDAR 1 mRNA expression in rats brain after I/R injury
Dong et al., 2009 [40]	Rats	15 Hz, 1 mA, 30 min/d, 5 d	Baihui (GV20)	2 h MCAO	~63%	EA pretreatment attenuates brain edema and BBB disruption, decreases MMP-9 expression and activity caused by subsequent cerebral ischemia
Wang et al., 2009 [41]	Rats, Mice	2/15 Hz, 1 mA, 30 min	Baihui (GV20)	2 h MCAO	~38%, 24 h, ~15%, 7days	EA pretreatment activates the endocannabinoid system
Du et al., 2010 [42]	Rats	2/15 Hz, 1 mA, 30 min	Baihui (GV20)	2 h MCAO	~18,24 h	ERK1/2 pathway is involved via CB1
Feng et al., 2010 [31]	Rats	2/15 Hz, 1 mA, 30 min/d, 5 d	Baihui (GV20)	+10 Gz, 5 min,	No morphological study	EA pretreatment attenuates the neuronal apoptosis, preserves neuronal morphology and inhibits the caspase-3 activity, ameliorates the learning and memory function
Ma et al., 2011 [43]	Rats	2/15 Hz, 1 mA, 30 min	Baihui (GV20)	2 h MCAO	~22%, 72 h	CB2 contributed to the delayed neuroprotection, whereas CB1 to the rapid ischemic tolerance
Wang et al., 2011 [44]	Rats	2/15 Hz, 1 mA, 30 min	Baihui (GV20)	2 h MCAO	~21%	EA pretreatment activates endogenous εPKC-mediated antiapoptosis via CB1

The electrical stimulation parameters and acupoints defining the protective effect of EA pretreatment are summarized. The infarct volume reduction induced by EA pretreatment is taken by percentage; most of them were estimated according to the bar graphs, for that the exact number of infarct size was not reported in the cited papers. The potential protective mechanisms discussed in the studies are also summarized. EA: electroacupuncture; ESP: electrical stimulation parameters; MCAO: middle cerebral artery occlusion; pCCAO: permanent common carotid artery occlusion; LADCA: left anterior descending coronary artery; SGIR: simulative global ischemia and reperfusion; K_ATP: ATP-sensitive potassium channel; A1R: Adenosine A1 receptor; 𝛽-AR: 𝛽-adrenoceptors; AC: adenylate cyclase; PKA: protein kinase A; cAMP: cyclic adenosine monophosphate; Glu: Glutamate; NMDAR: N-methyl-d-aspartate receptors; BBB: blood-brain barrier; MMP-9: matrix metalloproteinases-9; ERK1/2: extracellular regulated kinase 1/2; CB1: cannabinoid receptor type 1; CB2: cannabinoid receptor type 2; 𝜀PKC: epsilon protein kinase C.