Category I: Promotion of cell proliferation in CNS

Table S1: Neurogenesis

Target
Author (receptor/ Ac Selection Experimental #
Study title Publication Acupoints Animal Treatment Stage Results Conclusions
s molecule/ type reason model sessions
pathway)

A study on the Hindawi

effect of Publishing Immediately
neurogenesis and Corporation. after MCAO, 1. Ac. Improved CBF,
regulation of Evidence- Duration: Once 2. Enhanced
Ac enhances
GSK3B/PP2A Based daily for 3 neurogenesis by
neurogenesis via
expression in Complement GSK3β/ Shuigou Previous Permanent SD consecutive upregulating the
Luo, D MA Acute 3 regulation of
acupuncture ary and PP2A (+) (GV26) studies Left MCAO rats days; expression of GSK 3β
GSK-3 and PP2A
treatment of Alternative Stimulation: and PP2A in cortex,
expression
neural functional Medicine. Thrust/Lifted 3 hippocampus and
damage caused by Vol. 2014, times per/sec. striatum
focal ischemia in Article ID for 1 min.
MCAO rats 962343
1. EA increased
neuroblasts in the
ipsilateral SVZ and
hippocampus
Electroacupunctur (Subcallosal zone)
e promotes post- 5 days after and enhanced EA enhances
stroke functional Plos One MCAO; Freq: differentiation into proliferation and
Dazhui
recovery via February 2HZ; Int: 2V; neurons or differentiation of
BDNF/ (GV14), Not MCAO for Sub-
enhancing Kim, Y 2014 Volume EA Mice Time: 20min; 10 astrocytes, 2. EA neuronal stem
VEGF (+) Baihui specified 40 min acute
endogenous 9 Issue 2 Duration: 10 increased activation cells via the BDNF
(GV20)
neurogenesis in e90000 consecutive of BDNF and VEGF- and VEGF
mouse focal days mediated signaling pathway
cerebral ischemia downstream PI3K at
SVZ and
hippocampus, 3. EA
improved division of
NSCs
Electroacupunctur
e promotes 1. EA decreased EA promotes
neurological International Freq: 5/20Hz, infarct volume, 2. neurological
functional Journal of Zusanli Int: 2-4mA, promoted functional
recovery via the Hong, Molecular Retinoic (ST36), Previous Left MCAO SD Time: 20min, Not neurological recovery through
EA 28
retinoic acid J Medicine 31: Acid (+) Quchi studies for 120 min rats Duration: once specified functional recovery, modulating RA
signaling pathway 225-231, (LI11) a day for 4 and 3. increased RA expression and
in rats following 2013. weeks mRNA and protein stimulation of
cerebral ischemia- expression neurogenesis
reperfusion injury
Table S2: Cell proliferation in ischemic tissue

Target
Author (receptor/ Ac Selection Experimental #
Study title Publication Acupoints Animal Treatment Stage Results Conclusions
s molecule/ type reason model sessions
pathway)
Electro-acupuncture 1. EA improved
exerts beneficial 1 day neurological deficits, 2.
effects against after reduced infarct volume,
Zusanli EA promotes
cerebral ischemia International MCAO; 3. promoted proliferation
(ST36), the proliferation
and promotes the Journal of Freq: 1- of reactive astrocytes in
Wnt/β Quchi of neural
proliferation of Chen, Molecular Previous Left MCAO SD 20Hz; peri-infarct cortex, 4.
catenin EA (LI11) on Acute 3 stem/progenitor
neural progenitor B Medicine 36: studies for 120 min rats Time: enhanced proliferation of
(+) the cells via the
cells in the cortical 1215-1222, 30min; neural progenitor cells in
paretic Wnt/β-catenin
peri-infarct area 2015 Duration: peri-infarct cortex, and 5.
side pathway
through the Wnt/β- once daily promoted activation of
catenin signaling for 3 days Wnt pathway in peri-
pathway infarct cortex

EA may
promote
Freq: neurobehavioral
Electroacupuncture
40/60Hz; 1. EA improved recovery by
improves behavioral
Int: 1mA; behavioral recovery, 2. increasing the
recovery and Neurological Stem
Hegu Right Time: 15 upregulated positive cells protein and
increases SCF/c-kit Sciences Cell Not SD Not
Lu, T EA (LI4) MCAO for min; 7 and mRNA expression of mRNA
expression in a rat (2013) Factor specified rats specified
bilateral 120 min Duration: SCF, c-kit and MMP-9 expression of
model of focal 34:487–495 (+)
7 after cerebral SCF, c-kit and
cerebral
consecuti ischemia/reperfursion. MMP-9 after
ischemia/reperfusion
ve days cerebral
ischemia/reperf
usion.
 1 after
MCAO;
EA appears to
Zusanli Freq: 1-
Electroacupuncture 1. EA improved activate the
International (ST36), 20Hz;
promotes neural cell neurological function, 2. ERK1/2 signaling
Journal of Quchi Time:
proliferation in vivo Huan ERK1/2 Not Left MCAO SD reduced infarct volume, pathway to
Molecular EA (LI11) on 30min; Acute 3
through activation of g, J (+) specified for 120 min rats and 3. activated the protect against
Medicine 33: the Duration:
the ERK1/2 signaling ERK1/2 signaling pathway brain injury
1547-1553, paretic once a
pathway in ischemic brain cortex. during cerebral
2014 side day for 3
ischemia
consecuti
ve days
1. EA improved
2 h after neurological function, 2.
Electroacupuncture Zusanli
Experimental reperfusio reduced infarct volume,
at Quchi and Zusanli (ST36), EA enhances the
and n; Freq: 1- 3. activated the ERK1/2
treats cerebral Quchi activation of the
Therapeutic ERK 1/2 Clinical Left MCAO SD 20Hz; pathway in ischemic
ischemia-reperfusion Xie, G EA (LI11) on Acute 1 ERK1/2 pathway
Medicine 5: (+) use for 120 min rats Time: cerebral cortex and
injury through the and promotes
1593-1597, 30min; striatum, 4. promoted cell
activation of ERK paretic cell proliferation
2013 Duration: proliferation, and 5. EA
signaling side
single enhanced expression of
cyclin D1 and CDK4
1. EA improved
neurological deficits, 2.
reduced infarct volume,
Electro-acupuncture 3. improved motor EA promotes
at LI11 and ST36 function recovery, 4. the proliferation
acupoints exerts Zusanli Freq: 1- promoted reactive of reactive
Cell
neuroprotective Brain (ST36), 20Hz; astrocyte proliferation in astrocytes via
cycle
effects via reactive Research Quchi Previous Left MCAO SD Time: Not peri-infarct cortex and enhancement of
Tao, J proteins EA 3
astrocyte Bulletin 120 (LI11) on studies for 120 min rats 30min; specified striatum, 5. enhanced BDNF and
and
proliferation after (2016) 14–24 paretic Duration: expression of cell cycle promotes
BDNF (+)
ischemia and limb 3 days associated proteins expression of
reperfusion injury in (cyclin D1, CDK4, cell cycle
rats phospho Rb), and 6. EA proteins
promoted secretion of
BDNF from reactive
astrocytes
Category II: Regulation of CBF

Table S3: Angiogenesis

Target
Author (receptor/ Ac Selection Experimental #
Study title Publication Acupoints Animal Treatment Stage Results Conclusions
s molecule/ type reason model sessions
pathway)
45 min 1. EA enhanced
Effects of after expression of VEGF
electroacupuncture on Journal of MCAO; and Ang-1 in cortex
EA increases the
expressions of Traditiona VEGF, Freq: 40- around the ischemic
expression of
angiogenesis factors l Chinese Angioge Hegu Right 60Hz; Int: necrotic region,
Not Wistar angiogenesis factors
and anti-angiogenesis Ma, J Medicine nin 1 (+), EA (LI4) MCAO for 1.5V; Acute 7 lateral ventricle and
specified rats and inhibits the
factors in brain of 2008; Endostat bilateral 1h Time: dentate gyrus of
expression of anti-
experimental cerebral 28(3): in (-) 15min; hippocampus, and
angiogenesis factors
ischemic rats after 217-222 Duration: 2. EA reduced
reperfusion once daily expression of
for 7 days endostatin
Table S4: Vasoactive modulation

Target
Author (receptor, Ac Selection Experimental #
Study title Publication Acupoints Animal Treatment Stage Results Conclusions
s molecule, type reason model sessions
pathway)
1. EA increased
perfusion in the
cerebral cortex 2.
Immediat EA in the acute
Electroacupuncture increased ACh
ely after stage improves
acutely improves release and mAChR
ACh/ MCAO; ACh/eNOS-
cerebral blood flow Plos One Dazhui M3 expression in
Endothelial MCAO for Int: 1mA; mediated
and attenuates February 2013 (GV14), Not cerebral cortex, 3.
Kim, J nitric oxide EA 60 and 90 Mice Freq: 2Hz; Acute 1 perfusion
moderate ischemic Volume 8 Issue Baihui specified perfusion effects of
synthase min Time: augmentation,
injury via an 2 e56736 (GV20) EA were dependent
(+) 20min; improving tissue
endothelial on eNOS, 4. EA
Duration: and functional
mechanism in mice decreased infarct
single recovery
volume after
moderate ischemic
injury
EA significantly
1. EA reduced attenuates
neurological MCAO-induced
Electroacupuncture deficits, 2. increased increases in
improves cerebral Freq: CBF at the AngII expression
blood flow and BMC 15Hz; Int: ipsilateral and and its receptor-
attenuates Complementary Angiotensin 1mA, contralateral lesion mediated IP3
Shuigou Previous Right Wistar Not
moderate ischemic Li, J and Alternative II/AT1R (-), EA Time: 1 sites, 3. decreased signal
(GV26) studies MCAO rats specified
injury via Medicine 2014, AT2R (+) 20min; expression of AngII, transduction
Angiotensin II its 14:441 Duration: AT1R, and 4. EA pathway,
receptors-mediated single enhanced reduces
mechanism in rats expression of AT2R vasoconstriction
in ischemic core and and improves
penumbra regions blood supply in
ischemic region
Category III: Anti-apoptosis

Table S5: Specific apoptotic pathway

Target
Author (receptor/ Ac Selection Experimental #
Study title Publication Acupoints Animal Treatment Stage Results Conclusions
s molecule/ type reason model sessions
pathway)

1. Ac. suppressed Ac. exerts anti-

Acupuncture Starting on ischemia-induced apoptotic effects
suppresses the third day increases in c-Fos in the
Zusanli Common
ischemia-induced of the and caspase 3 hippocampal CA1
Neuroscience (ST36) carotid
increase in c-Fos Jang, Caspase Not experiment; Sub- TUNEL cells in the region by
Letters 347 MA bilateral, artery Gerbils 16
expression and M 3 (-) specified Time: 20min; acute hippocampal CA1 suppressing
(2003) 5-8 Hegu (LI4) occlusion
apoptosis in the Duration: region, 2. The most ischemia-induced
bilateral for 5 min
hippocampal CA1 Twice daily potent inhibitory increments in c-
region in gerbils for 8 days effect was observed Fos and caspase 3
at Zusanli acupoint cells

1. Ac improved
Morris water maze Ac improves
Starting 16
trial performance, memory via anti-
Acupuncture Tanzhong days after
2. Ac significantly apoptotic effects
protected cerebral (CV17), Right artery
reduced the in hippocampal
multi-infarction rats Zhongwan common occlusion;
number of CA1 region by
from memory Physiology & (CV12), carotid Stimulation:
apoptotic cells in downregulating
impairment by Wang, Behavior 96 Bax (-) - Qihai Not artery and Wistar twisted twice
MA Chronic 21 hippocampal CA1 the expression of
regulating the T (2009) 155– Bcl-2 (+) (CV6), specified external rats a sec. for 30
region, 3. Ac pro-apoptotic
expression of 161 Zusanli carotid sec. in each
upregulated Bcl-2 factor Bax and
apoptosis related (ST36), artery point;
expression, and 4. upregulating the
genes Bcl-2 and Bax Xuehai occlusion Duration:
Ac counter- expression of
in hippocampus (SP10) Once daily
regulated the anti-apoptotic
for 21 days
expression of pro- factor Bcl-2
apoptotic Bax
 1. EA increased
Potentiation of Akt
expression of AKT
and suppression of
Just after mainly in the
caspase-9 EA activates Akt
Neuroscience Baihui MCAO; Freq: ischemic penumbra,
activations by Akt (+), Right and suppresses
Wang, Letters (GV20), Not Wistar 20/3Hz; Int: 2. EA diminished
electroacupuncture caspase EA MCAO for Acute 1 caspase 9
S 331(2002) Renzhong specified rats 3mA; Time: caspase 9 induction,
after transient 9 (-) 90 min inhibiting
115–118 (GV26) 1h; Duration: and 3. EA decreased
middle cerebral apoptotic cascade
single number of TUNEL
artery occlusion in
positive cells in the
rats
cortex
1. EA reduced
infarct size, 2.
diminished the
number of
apoptotic cells in EA
DR5 Immediately ischemic tissue, 3. neuroprotective
Effects of International
extrinsic after MCAO; reversed the effects may be
electroacupuncture Journal of Baihui
and Right Freq: 2Hz; increase in associated with
on apoptotic Molecular (GV20), Previous
Kim, Y intrinsic EA MCAO for SD rats Int: 1mA; Acute 2 expression of DR5, the inhibition of
pathways in a rat Medicine 32: Qihai studies
pathway 90 min Time: 30min; 4. EA enhanced DR and
model of focal 1303-1310, (CV6)
mediator Duration: expression of Bcl-2, mitochondrial
cerebral ischemia 2013
s (-) Twice a day Bcl-xL, cIAP1 and 2, apoptotic
and 5. EA decreased pathways
expression and
activities of
caspase-3, -8, and -
9
Table S6: Non-specific apoptotic pathway

Target
Author (receptor/ Ac Selection Experimental #
Study title Publication Acupoints Animal Treatment Stage Results Conclusions
s molecule/ type reason model sessions
pathway)
1. EA improves
neurological
deficits, 2. EA
Electroacupuncture
reduces infarct
at the Quchi and
volume, 3. EA EA exerts
Zusanli acupoints 120 min
Zusanli activates the neuroprotective
exerts International after MCAO;
(ST36), PI3K/Akt function in
neuroprotective Journal of Freq: 1 and
Chen, PI3K/Akt Quchi Left MCAO SD pathway, 4. EA ischemic stroke
role in cerebral Molecular EA Clinical use 20Hz; Time: Acute 1
A (+) (LI11) on for 120 min rats increases via activation of
ischemia Medicine 30: 30min;
the non expression of the PI3K/Akt
reperfusion injured 791-796, 2012 Duration:
paretic limb BDNF and GDNF, anti-apoptotic
rats via activation of single
and 5. EA pathway
the PI3K/Akt
upregulates anti-
pathway
apoptotic Bcl-
2/Bax ratio in
ischemic tissue
1. EA improved
neurological
deficit scores, 2.
reduced infarct
EA exerts a
volume, 3.
neuroprotective
reduced
effect on
apoptosis in
Electroacupuncture cerebral
1 day after penumbra of
at points of Zusanli Zusanli ischemia
MCAO; Freq: cerebral cortex,
and Quchi exerts (ST36), through the
Neuroscience 4-20Hz; 4. EA stimulated
anti-apoptotic PI3K/Akt Quchi Left MCAO SD activation of the
Xue, X Letters 558 EA Clinical use Time: 30min; Acute 2 expression of
effect through the (+) (LI11) on for 120 min rats PI3K/Akt
(2014) 14– 19 Duration: PI3K and p-Akt in
modulation of the paretic pathway,
once a day ischemic cortex,
PI3K/Akt signaling limb inhibiting
for 2 days 5. EA
pathway apoptosis in the
upregulated
penumbra of
levels of p-Akt
cerebral
and Bcl-2, 6. EA
ischemic cortex
weakened the
downregulation
of p-Bad and Bcl-
2, and reduced
 the upregulation
of Bax, and 7. EA
enhanced the
ratios of the
protein of p-
Bad/Bad and
anti-apoptotic
Bcl-2/Bax
1. EA reduced
Electroacupuncture
infarct volume, 2.
-like stimulation at
EA lowered EA elicits BDNF-
Baihui and Dazhui
neurological mediated
acupoints exerts Following
deficit scores, 3. neuroprotective
neuroprotective MCAO; Freq:
EA enhanced action against
effects through MEK1/2/ 5Hz; Int: 2.7-
Chinese BDNF expression caspase-3-
activation of the Complementary ERK1/2/ Baihui 3mA; Time:
Medicine Right in ischemic dependent
brain-derived Cheng and Alternative p90RSK/ (GV20), SD 25min;
EA theory - MCAO for Acute 4 cortex, 4. EA neuronal
neurotrophic ,C Medicine 2014, bad Dazhui rats Duration:
Previous 15 min suppressed apoptosis
factor-mediated 14:92 pathway (GV14) twice daily
studies increase of through
MEK1/2/ERK1/2/p9 (+) for 2
caspase-3, and 5. activation of the
0RSK/bad signaling consecutive
EA enhanced Raf-
pathway in mild days
expression of 1/MEK1/2/ERK1
transient focal
protein kinases /2 pathway
cerebral ischemia in
related to the
rats
ERK1/2 pathway
1. EA reduced EA provides
infarct volume, 2. neuroprotection
EA improved by
neurological downregulation
Electroacupuncture deficits, 3. EA of astrocytic
-like stimulation at lowered S100B, S100B
After MCAO;
the Baihui (GV20) p38 MAP kinase- expression,
Freq: 5Hz;
and Dazhui (GV14) mediated NF-kB, delaying infarct
Chinese Int: 2.7-3mA;
acupoints protects Plos One March Baihui and iNOS expansion
Medicine Right Time: 25min;
rats against Cheng 2014, Volume (GV20), SD expression, 4. EA through the
S100B (-) EA theory - MCAO for Duration: Acute 6
subacute-phase ,C 9, Issue 3, Dazhui rats downregulated modulation of
Previous 15 min once daily
cerebral ischemia- e91426 (GV14) TNF- p38 MAP
studies for 6
reperfusion injuries α/TRADD/FADD/ kinase-mediated
consecutive
by reducing S100B- cleaved caspase- NF-kB
days
mediated 8/cleaved expression,
neurotoxicity caspase-3 attenuating
apoptotic oxidative/nitrati
pathway in ve stress and
ischemic cortical downregulating
penumbra, 5. EA the TNF-
 downregulated a/TRADD/FADD/
S100B/ cleaved
nitrotyrosine caspase-
8/cleaved
caspase-3
apoptotic
pathway

1. EA reduced
infarct volume, 2.
EA
EA reduced
downregulates
neurological
reactive
deficit scores, 3.
astrocytosis to
EA
provide
downregulated
neuroprotection
GFAP expression,
by activating the
Electroacupuncture 4. EA activated
p38 MAPK/CREB
at different 1 day after p38 MAPK/CREB
pathway. The
frequencies (5Hz MCAO; Freq: pathway, 5. EA
modulating
and 25Hz) 5-25Hz; Int: upregulated
Chinese effects of EA on
ameliorates Complementary Baihui 2.7-3mA; expression of Bcl-
p38 Medicine Right Bax-mediated
cerebral ischemia- Cheng and Alternative (GV20), SD Time: 25min; xL and Bcl-1, 6.
MAPK/ EA theory - MCAO for Acute 7 apoptosis are
reperfusion injury in ,C Medicine 2015 Fengfu rats Duration: EA
CREB (+) Previous 30 min possibly due to
rats: possible 15:241 (GV16) once daily downregulated
studies the activation of
involvement of p38 for 7 expression of
Bcl-xL and Bcl-2
MAPK-mediated consecutive Bax, 7. EA
signaling,
anti-apoptotic days decreased
thereby
signaling pathways Smac/DIABLO
preventing
translocation, 8.
Smac/DIABLO
EA decreased
translocation
caspase-3
and restoring
upregulation, 9.
XIAP-mediated
EA enhanced
caspase-3
XIAP expression
inhibition
(all the results
were shown at
 the ischemic
cortical
penumbra)

1. EA improved
neurological
deficit scores and
reduced
cognitive
Electroacupuncture
impairment
ameliorates
2 h after (learning and
cognitive
Molecular MCAO; Freq: memory), 2. EA
impairment through Baihui Chinese EA inhibits NF-
Medicine NF-kB 1-20Hz; reduced infarct
inhibition of NF-kB Feng, (GV20), Medicine Left MCAO SD κB-mediated
Reports 7: pathway EA Time: 30min; Acute 10 volume, 3. EA
mediated neuronal X Shenting theory - for 120 min rats neuronal cell
1516-1522, (-) Duration: inhibited
cell apoptosis in (GV24) Clinical use apoptosis
2013 daily for 10 apoptosis by
cerebral ischemia-
days blocking NF-кB
reperfusion injured
pathway and
rats
downregulating
the apoptotic
Fas/Bax genes
expression in
ischemic tissue
 1. EA reversed
TRPM7 over-
expression in
ischemic cortex
and hippocampal
EA can reverse
Electroacupuncture Immediately CA3 and CA1
the increase of
regulates TRPM7 after MCAO; regions, 2. EA
Renzhong Xingnao TRPM7 by
expression through Life Sciences 81 Right Freq: 16-4Hz; upregulated the
Zhao, TRPM7 (GV26), Kaiqiao SD enhancing trkA
the trkA/PI3K (2007) 1211– EA MCAO for Int: 1-3V; Acute 1 expression of
L (-) Chengjiang acupuncture rats activity, which
pathway after 1222 30 min Time: 30min; trkA in the same
(CV24) method triggers the
cerebral ischemia– Duration: regions, 3. trkA
downstream
reperfusion in rats single triggered the
PI3K pathway
downstream PI3K
pathway,
necessary for the
effect of EA on
TRPM7
EA effectively
inhibits the
Electroacupuncture 1. EA improved overexpression
Journal of
effect on neurological of JAK2,
Traditional Baihui
neurological Freq: 20Hz; Not deficits, 2. EA blocking the
Chinese (GV20), SD
behavior and Liu, R JAK2 (-) EA Not specified MCAO Int: 1-2mA; specifi 1 lowered the signal
Medicine 2012 Dazhui rats
tyrosine kinase-JAK Time: 30min ed overexpression transduction
September 15; (GV14)
2 in rats with focal of JAK2 in the pathways
32(3): 1-2
cerebral ischemia ischemic cortex induced by JAK2
(neuronal
apoptosis)
1. EA improved
neurological
deficits, 2. EA
diminished EA alleviates
1.5 h after
Effect of cerebral I/R neurological
MCAO; Freq:
electroacupuncture Evidence-Based Chize injury, deficits, reduces
2-15Hz; Int:
on cell apoptosis Complementary (LU5)+Hegu particularly in the the apoptosis
2mA; Time:
and ERK signal and Alternative (LI4); CA1 index, and
Left MCAO SD 20min;
pathway in the Wu, C Medicine, ERK (+) EA Zusanli Clinical use Acute 3 hippocampus simultaneously
for 30 min rats Duration:
hippocampus of Volume 2015, (ST36)+ area, 3. EA upregulates the
once daily
adult rats with Article ID Sanyinjiao reduced the expression of p-
for 3
cerebral ischemia- 414965 (SP6) apoptosis index, ERK signaling
consecutive
reperfusion and 4. EA pathway in I/R
days
upregulated rats
expression of p-
ERK signaling
pathway
Category IV: Regulation of neurochemicals

Table S7: Neurotransmitters and receptors

Target
(receptor/m Ac Selection Experimental #
Study title Authors Publication Acupoints Animal Treatment Stage Results Conclusions
olecule/ type reason model sessions
pathway)
1. Ac did not
Acupuncture
improve
stimulation at
cognitive and
Baihui acupoint Ac increases
memory deficits
reduced cerebral The American levels of
Immediately in rats with
infarct and Journal of Chinese dopamine
after MCAO; ischemia
increased dopamine Chinese Medicine Right reducing the
Chuang, Dopamine Baihui Time: 20min; reperfusion
levels in chronic Medicine, Vol. MA theory - MCAO for SD rats Acute 12 degree of
C (+) (GV20) Duration: 3 injury, 2. Ac
cerebral 35, No. 5, Previous 90 min cerebral
times a week increased
hypoperfusion and 779–791, studies atrophy after
for 4 weeks dopamine
ischemia- 2007 cerebral
levels in the
reperfusion injured infarct
right cerebral
Sprague-Dawley
cortex and
rats
hippocampus
1. EA increased
GABA in
15 min after cerebral cortex
EA up-
MCAO; Freq: and
Role of GABA in regulates
3.58-6.25Hz; hippocampus
electro- GABA
Int: 1.4-2mA; CA1 region, 2.
acupuncture Neuroscience Shuigou expression in
Time: 60min EA reduced
therapy on cerebral Letters 383 (GV26), Not Left MCAO the ischemic
Gan, P GABA (+) EA SD rats with a 10 Acute 1 infarct size, 3.
ischemia induced by (2005) 317– Baihui specified for 120 min cerebral
min pause EA increased
occlusion of the 321 (GV20) cortex and
every 30 the percentage
middle cerebral CA1
min; of surviving
artery in rats hippocampus
Duration: neurons in the
area
single ipsilateral
cerebral cortex
and striatum
 1. Ac improved
performance in
behavioral
tests, 2. AC
Acupuncture Stimulation: reduced infarct AC improves
improves locomotor Rotated volume, 3. AC locomotor
function by clockwise 2-3 increased β- function by
Neuroscience GABA
enhancing GABA Previous Right times per Not endorphin modulating
Xu, Q Letters 588 receptors MA Jiaji (EX-B2) SD rats 7
receptor expression studies MCAO sec; Time: specified concentrations the
(2015) 88–94 (+)
in transient focal 30sec; in striatum and expression of
cerebral ischemia Duration: 7 spinal cord, and GABA
rats days 4. Ac increased receptors
expression of
GABA receptors
in striatum and
spinal cord
EA
1. EA depressed
suppresses
The American glutamate
Electroacupuncture Bilateral Immediately both
Journal of release in CA1
Attenuates Both Fengfu common after hyperemia
Chinese hippocampal
Glutamate Release Glutamate (GV16), Not carotid ischemia; and excessive
Pang, J Medicine, Vol. EA Gerbils Acute 1 subfield, 2. EA
and Hyperemia (-) Shendao specified artery Freq: 7Hz; glutamate
31, No. 2, suppressed
After Transient (GV11) occlusion Int: 6mA; release
295–303, hyperemia
Ischemia in Gerbils for 5 min Time: 30min during and
2003 during
after
reperfusion
ischemia
EA prolongs
the time
windows of
the
Electroacupuncture 1. EA reduced expression of
Immediately
regulates NMDA NR1 levels in TrkA in
after MCAO;
receptor NR1 Brain Renzhong ischemic ischemic
NMDA Right Freq: 16-4Hz;
subunit expression Research 1064 (GV26), Not cortical areas cortex. EA
Sun, N receptor EA MCAO for SD rats Int: 1-3V; Acute 1
via PI3-K pathway in (2005) 98– Chengjiang specified through PI3K, 2. also reverses
(-) 30 min Time: 30min;
a rat model of 107 (CV24) EA increased the
Duration:
cerebral ischemia– TrkA in cortical expression of
single
reperfusion ischemic areas the NR1
subunit
through the
PI3-K
pathway
Table S8: Antioxidant enzymes

Target
Author (receptor/ Ac Experimental #
Study title Publication Acupoints Selection reason Animal Treatment Stage Results Conclusions
s molecule/ type model sessions
pathway)

9 days after
Tanzhong occlusion;
Ac exerts
(REN17), Stimulation:
beneficial
Zhongwan twisted twice 1. Ac
Acupuncture Internal effects on
(REN12), Yiqitiaoxue- a sec. for 30 significantly
prevents cognitive Neuroscience carotid spatial
SOD/ GSH- Qihai Fubenpeiyuan Wistar sec. in each Sub- increased
deficits and oxidative Liu, C Letters 393 MA occlusion 18 memory and
Px (+) (REN6), acupuncture rats point; acute hippocampal
stress in cerebral (2006) 45–50 over 1-2 antioxidant
Zusanli method Duration: SOD and GSH-
multi-infarction rats min status of
(ST36), Once daily Px activity
cerebral multi-
Xuehai for 21 days
infarction rats
(SP10) (rest every 7
days)
 1. Ac
ameliorated
neurological
3 days after
impairment, 2.
occlusion; Ac plays a
Ac reduced
Stimulation: neuro-
infarct size, 3.
Acupuncture elicits Twirling protective
Ac suppressed
neuroprotective Scientific manipulation effect against
Bilateral overproductio
effect by inhibiting Reports, Common >60 in 30 cognitive
Zusanli n of O2 via
NAPDH oxidase- December NADPH carotid Wistar sec; Sub- impairment via
Shi, G MA (ST36), Not specified 13 inhibition of
mediated reactive 2015, oxidase (-) artery rats Duration: acute inhibition of
Baihui NADPH
oxygen species 5:17981, DOI: occlusion once daily NAPDH
(GV20) oxidase in the
production in 10.1038 for 2 weeks oxidase-
hippocampus,
cerebral ischemia (1 day rest mediated
and 4. Ac
after 6 days oxidative
suppressed
of stress
expression of
treatment)
NADPH
oxidase
subunits

Electroacupuncture EA reduces the

reduces the extent of 30 min after extent of lipid
lipid peroxidation by MCAO; Freq: 1. EA peroxidation in
Neuroscience
increasing superoxide Antioxidant Fengchi Right 2Hz; Int: increased SOD ischemic-
Letters 354
dismutase and Siu, F enzymes EA (GB20) Not specified MCAO for SD rats 0.7V; Time: Acute 1 and GSH-Px reperfused rat
(2004) 158–
glutathione (+) bilateral 1h 30min; activity in brains, possibly
162
peroxidase activities Duration: ischemic brain by increasing
in ischemic single the activities of
reperfused rat brains SOD and GPx
1. EA reduced
Immediately neurological
EA improves
after MCAO; deficits, 2.
respiratory
Neurochemical Freq: improved
Advance chain function
mechanism of 5/20Hz; Int: mitochondrial
Access Renzhong and has an
electroacupuncture: Respiratory Right 2-4mA; Time: respiratory
Zhong Publication 27 (GV26), anti-oxidative
anti-injury effect on chain EA Not specified MCAO for SD rats 60min with Acute 1 control ratio in
,S October 2007 Baihui action in brain
cerebral function enzymes 90 min 15 min rest penumbra
eCAM 2009; (GV20) tissues at the
after focal cerebral every 20 area, and 3.
6(1)51–56 infarct
ischemia in rats min; EA increased
penumbra
Duration: the activities
zone
single of succinic
dehydrogenas
 e, NADH
dehydrogenas
e and
cytochrome C
oxidase in
penumbra
zone

EA can
Electroacupuncture upregulate the
potentiates the 1. EA activity of Trx
30 min after
disulphide-reducing increased TR system by
Fengchi MCAO; Freq:
activities of activity with increasing the
Life Sciences (GB20), Right 2Hz; Int:
thioredoxin system Thioredoxin St36, 2. EA availability of
Siu, F 77 (2005) EA bilateral Clinical use MCAO for SD rats 0.7V; Time: Acute 1
by increasing (+) upregulated Trx to TR and
386–399 Zusanli 1h 30min;
thioredoxin expression of thereby
(ST36) Duration:
expression in Trx at both reduce the
single
ischemia-reperfused acupoints ROS-induced
rat brains formation of
disulphides

Table S9: Inflammatory mediators

Target
Author (receptor/ Ac Selection Experimental #
Study title Publication Acupoints Animal Treatment Stage Results Conclusions
s molecule/ type reason model sessions
pathway)

Effects of After 2 h
acupuncture at MCAO;
Baihui (DU20) and Chinese Freq: 2Hz; Ac delays
Zusanli (ST36) on Journal of Left Chinese Int: 1mA; inflammatory
1. Ac reduced the
the expression of Integrative Zusanli Medicine Right Time: injury, which was
HSP70/ SD expression of HSP70
heat shock protein Xu, H Medicine EA (ST36), theory - MCAO for 20min; Acute 7 associated with a
TNFα (-) rats and TNF-α protein in
70 and tumor 2014 Baihui Clinical 2h Duration: reduction in the
the peripheral serum
necrosis factor α in May;20(5):3 (GV20) use once a expression of
the peripheral 69-374 day (7 HSP70 and TNF-α
serum of cerebral times in
ischemia- total)
 reperfusion-injured
rats

1. EA improved
neurological function,
Electroacupuncture 2. reduced infarct EA reduces
exerts anti- volume, 3. alleviated ischemic brain
Zusanli 2 h after
inflammatory cerebral damage, improves
International (ST36), MCAO;
effects in cerebral inflammation, 4. neurological
Journal of Quchi Freq: 1-
ischemia TLR4/ Clinical Left MCAO SD suppressed activation deficits and exerts
Lan, L Molecular EA (LI11) on 20Hz; Int: Acute 1
reperfusion injured NF-kB (-) use for 120 min rats of the TLR4/NF-kB anti-inflammation
Medicine 31: the 0.01mA;
rats via pathway by inhibiting activity via
75-80, 2013 paretic Duration:
suppression of the NF-kB nuclear inhibition of the
limb 1 day
TLR4/NF-kB translocation, and 5. TLR4/NF-κB
pathway EA inhibited I/R- pathway
induced secretion of
TNFα, IL-1β, IL-6

Table S10: Neurotrophic factors

Target
Author (receptor/ Ac Selection Experimental #
Study title Publication Acupoints Animal Treatment Stage Results Conclusions
s molecule/p type reason model sessions
athway)
 Electroacupuncture
Baihui 1. EA improved
enhances motor Freq: 3Hz;
(GV20), motor recovery, EA increases
recovery Acupuncture Time:
on the 2. enhanced the expression
performance with in Medicine Right 5min;
Kim, non Not SD Not expression of of BDNF and
brain-derived Journal BDNF (+) EA MCAO for Duration: 6
M paretic specified rats specified BDNF in the improves
neurotrophic factor 2012;30:222– 2h every 2
side ischemic lobe, motor
expression in rats 226 days for 2
Qubin and 3. EA recovery
with cerebral weeks
(GB7) increased TrkB
infarction

Table S11: Anaerobic metabolism

Target
Author (receptor/ Ac Selection Experimental #
Study title Publication Acupoints Animal Treatment Stage Results Conclusions
s molecule/ type reason model sessions
pathway)
 EA improves neurological
1. EA promoted
deficits through
After 2h recovery of
Electroacupuncture activating the lactate
of MCAO; neurological deficits, 2.
up-regulates metabolism in the
Bilateral Freq: increased lactate
astrocytic MCT1 Life ischemic brain area and
Neiguan 2/15Hz; concentrations in the
expression to Sciences up-regulating the
Lactate (PC6), Not Wistar Int: 1mA; ischemic brain, 3.
improve Lu, Y 134 EA MCAO Acute 7 astrocytic expression of
(+) bilateral specified rats Time: enhanced expression of
neurological deficit (2015) MCT1 to facilitate the
Quchi 20min; MCT1 in astrocytes, and
in middle cerebral 68–72 transfer of intracellular
(LI11) Duration: 4. EA increased GFAP
artery occlusion lactate to the
once daily expression in the
rats extracellular domain to
for 7 days ischemic area, mainly at
be used by injured
the hippocampus
neurons

Category V: Memory improvement

Table S12: LTP modulation

 Target
Author (receptor/ Ac Selection Experimental #
Study title Publication Acupoints Animal Treatment Stage Results Conclusions
s molecule/ type reason model sessions
pathway)
1. Ac improved
3 days after
hippocampal-dependent
occlusion;
memory, 2. Ac. reversed Acupuncture
Stimulation:
impairment of LTP in improves
Hippocampal Turned two
hippocampal PP-DG by cognitive
cAMP/PKA/CREB is Physiology & Right spins per
cAMP/ Zusanli upregulating hippocampus
required for Behavior 139 Previous internal Wistar second for Sub-
Li, Q PKA/ MA (ST36) 13 cAMP/PKA/CREB function by
neuroprotective (2015) 482– studies carotid rats 30 seconds; acute
CREB (+) bilateral pathway, 3. Ac. modulating the
effect of 490 occlusion Duration:
significantly inhibited cAMP/PKA/CRE
acupuncture once daily
PDE activity, and 4. Ac. B signaling
for 14 days
enhanced ERK pathway
(rest every 7
expression in CA1 and
days)
DG regions
Electroacupuncture
at Baihui acupoint
(GV20) reverses
1. EA improved behavior
behavior deficit and Journal of 1 day after
deficit, 2. EA restored EA improves
long term Integrative MCAO; Freq:
LTP in hippocampal CA1 vascular
potentiation Neuroscience. NR1- Right 2Hz; Int:
Baihui Previous areas, 3. EA decreased dementia by
through N-Methyl- Lin, Y Volume 9, TRPV1 EA MCAO for SD rats 2mA; Time: Acute 6
(GV20) studies NR1 and TRPV1 levels in decreasing the
D-Aspartate and Number 3, (-) 10 min 20min;
hippocampal CA1 areas expression of
transient receptor September Duration: 6
(pyramidal neurons) to NR1-TRPV1
potential vanilloid 2010, 269-282 days
basal conditions
subtype 1 receptors
in middle cerebral
artery occlusion rats