Table 1 Characteristics of the 34 included studies.

From: Acupuncture for neurogenesis in experimental ischemic stroke: a systematic review and meta-analysis

Study (years)

Species (Sex, n = experimental /control group )

Weight

Model (method)

Anesthetic

Treatment group (Method to acupuncture)

Control group

Neurogenesis

Outcome Index (time)

Intergroup Differences

Huang 2009 (11)

Wistar rats (male, 15/15)

200 ± 20 g

MCAO/ 2 h

6% chloralhydrate (35 mg/100 g)

EA 30 min after reperfusion per day, with frequency of 20 Hz and current density of 1–2 mA (baihui, dazhui)

Non-EA

Proliferation, migration, differentiation

1. NFS (ZL, 7, 14, 28d); 2. Brdu+ cells; 3. PSA-NCAM+ cells; 4. Brdu/NeuN+ cells.

1. P < 0.01; 2. P < 0.05 (7, 14d), P > 0.05 (28d); 3. P < 0.05 (7, 14d), P > 0.05 (28d); 4. P < 0.05 (7, 14d), P > 0.05 (28d).

Yan 2008 (12)

SD rats (male, 12/12)

200–250 g

MCAO/30 min

10% chloralhydrate (0.3 ml/100 g)

EA 5 min after reperfusion per day (shuigou, neiguan, quchi, zusanli)

Non-EA

Differentiation

1. CyclinD1 level (2d, 7d); 2. GFAP level

1. P < 0.05, P > 0.05; 2. P < 0.05, P < 0.01

Ren 2007 (13)

SD rats (male, 9/9)

200 ± 20 g

PermanentMCAO (Tamura)

10% chloralhydrate (3.5 ml/1 Kg)

EA 20 min after surgery per day, with frequency of 15 Hz and current density of 1–3 mA (baihui, renzhong)

Non-EA

Proliferation, differentiation

1. NFS (Bederson, 7d); 2. Nestin+ cells; 3. PNCA+ cells; 4. Vimentin+ cells; 5. Tuj-1+ cells;

1. P < 0.05; 2. P < 0.01; 3. P < 0.01; 4. P < 0.01; 5. P < 0.01.

Gao 2010 (14)

SD rats (male, 30/30)

450–600 g

MCAO/3 h (ZL)

10% chloralhydrate (0.3 ml/100 g)

EA 10 min after reperfusion at once, 1 h, 2 h and then per day (jianyu, biguan, zusanli, waiguan)

Non-EA

Proliferation, differentiation

1. NFS (1, 3, 7, 14, 21d); 2. BWC; 3. Brdu+ cells; 4. Brdu/NeuN+ cells; 5.Brdu/GFAP+ cells;

1. P < 0.01 (3, 7, 14, 21d); 2. P < 0.01 (1, 3, 7d); 3. P < 0.01; 4. P < 0.01; 5. P < 0.05 (3, 7, 14d);

Luo 2007 (15)

Wistar rats (male, 18/18)

250 ± 10 g

MCAO/2 h

10% chloralhydrate (35 mg/100 g)

EA 20 min after reperfusion per day, with frequency of 30/100 Hz and current density of 6–15 V (Du: renzhong, baihui)

Non-EA

Proliferation

1. NFS (ZL, 7, 14, 28d); 2. Brdu+ cells; 3. Brdu/Nestin+ cells

1. P < 0.01; 2. P < 0.01 (14, 28d), P > 0.05 (7d); 3. P < 0.01 (14, 28d), P > 0.05 (7d);

     

(Rendu: chengjiang, shenyu, guanyuan, renzhong, baihui)

  

2. Brdu+ cells; 3. Brdu/Nestin+ cells

2. P < 0.01; 3. P < 0.01

Yang 2010 (16)

Wistar rats (male, 18/18)

NR

MCAO

NR

EA 10 min after surgery per day (guanyuan, qihai, chengjiang)

Non-EA

Proliferation

1. EGFPP/Nestin+ cells (7, 14, 28d)

1. P < 0.01

Rui 2011 (17)

Wistar rats (male, 20/20)

250 ± 30 g

MCAO/2 h (ZL)

10% chloralhydrate (0.3 ml/100 g)

EA 30 min after reperfusion per day, with frequency of 10 HZ and current density of 3–5 mA (baihui, fengfu)

Non-EA

Differentiation

1. Brdu/NSE+ cells (3, 7, 14, 21d); 2. Brdu/GFAP+ cells

1. P < 0.01; 2. P < 0.01.

Li 2012 (18)

SD rats (20/20)

210–250 g

MCAO/2 h (ZL)

4% chloralhydrate

EA 30 min after reperfusion per day, with frequency of 5–10 HZ and current density of 2 mA (quchi, zusanli)

Non-EA

Proliferation

1. NFS (NSS, 3, 5, 7, 14d); 2. Brdu+ cell; 3. Nestin+ cell.

1. P < 0.05 (5, 7, 14d); 2. P < 0.05; 3. P < 0.05.

Wang 2013 (19)

SD rats (male, 12/12)

250–300 g

MCAO/2 h (ZL)+ transplantation of BMSC

4% chloralhydrate

EA 30 min after reperfusion per day, with frequency of 2–15HZ and current density of 1 mA (baihui, shuigou)

Non-EA+ transplantation of BMSC

Proliferation

1. NFS (mNSS, 7, 14d); 2. Infarct volume; 3. Brdu+ cell; 4. NSE+ cell.

1. P < 0.05; 2. P < 0.05 (14d); 3. P > 0.05; 4. P < 0.01 (14d)

Tang 2008 (20)

Wistar rats (12/12)

250–300 g

MCAO

10% chloralhydrate (35 mg/Kg)

EA 15 min after surgery per day, with frequency of 5–10 HZ and current density of 2 mA (quchi, zusanli)

Non-EA

Differentiation

1. Dil/Brdu/NeuN+ cell (7, 14, 21d); 2. Dil/Brdu/GFAP+ cell

1. P < 0.05; 2. P < 0.05

Liu 2001 (21)

SD rats (male, 20/20)

250–280 g

Permanent MCAO

1% pentobarbital sodium

EA 30 min after surgery per day, with frequency of 5–10 HZ and current density of 1–5 mA (baihui, dazhui)

Non-EA

Proliferation

1. NFS (Bederson, 3, 7, 14, 21d); 2. Brdu+ cells.

1. P < 0.05; 2. P < 0.05

Tao 2008 (22)

SD rats (male, 27/27)

250 ± 30 g

MCAO/2 h (ZL)

10% chloralhydrate (0.3 ml/100 g)

EA 30 min after reperfusion per day, with frequency of 1–20 HZ and current density of 6 V (quchi, zusanli)

Non-EA

Proliferation, differentiation

1. Brdu+ cells (4, 7, 14d); 2. Brdu/NeuN+ cells; 3. Brdu/GFAP+ cells.

1. P < 0.05 (7d); 2. P > 0.05; 3. P < 0.05 (7d).

Diao 2008 (23)

Wistar rats (male, 23/26)

250 ± 10 g

MCAO/2 h (ZL)

10% chloralhydrate (350 mg/Kg)

EA 20 min after reperfusion per day, with frequency of 30–100 HZ and current density of 6–15 V (chengjiang, qihai, guanyuan)

Non-EA

Proliferation

1. Brdu+ cells (7, 14, 28d); 2. Brdu/Nestin+ cells.

1. P < ;0.01; 2. P < 0.05/0.01).

Yang 2006 (24)

Wistar rats (male, 18/18)

250 ± 20 g

MCAO/2 h

10% chloralhydrate (350 mg/Kg)

EA 10 min after reperfusion per day,(chengjiang, qihai, guanyuan)

Non-EA

Proliferation, differentiation

1. Brdu+ cells (7, 14, 28d); 2. Brdu/GFAP+ cells; 3. Brdu/Nestin+ cells.

1. P < 0.01 (14, 28d); 2. P < 0.01 (28d); 3. P < 0.05 (14, 28d).

Song 2008 (25)

SD rats (male, 12/12)

250–300 g

MCAO/30 min (Koizumi)

10% chloralhydrate (3 ml/Kg)

MA 20 min after reperfusion per day,(shuigou, neiguan, quchi, zusanli)

Non-MA

Differentiation.

1. NFS (Bederson, 2, 7d); 2. GFAP level.

1. P < ;0.05 (7d); 2. P < 0.01 (7d).

Yang 2008 (26)

Wistar rats (male, 30/30)

250 ± 10 g

MCAO/2 h

10% chloralhydrate (35 mg/100 g)

EA 20 min after reperfusion per day, with frequency of 30/100 Hz and current density of 5 V (Du: renzhong, baihui)

Non-EA

Differentiation.

GFAP+ cells (7, 14, 28d)

P < 0.05 (14, 28d)

     

(Rendu: chengjiang, guanyuan, renzhong, baihui)

  

GFAP+ cells

P < 0.05 (14, 28d)

Pi 2006 (27)

Wistar rats (male, 22/24)

250 ± 10 g

MCAO/2 h + bFGF

10% chloralhydrate (35 mg/100 g)

EA 20 min after reperfusion per day, with frequency of 30/100 Hz and current density of 6–15 V (chengjiang, qihai, guanyuan)

Non-EA + bFGF

Proliferation

1. Brdu+ cells (7, 14, 28d); 2. Brdu/Nestin+ cells.

1. P < 0.05; 2. P < 0.05.

Ye 2012 (28)

Wistar rats (male, 60/60)

250 ± 30 g

MCAO

2% pentobarbital sodium (45 mg/Kg)

EA 15 min after surgery per day, with frequency of 5 Hz and current density of 2 mA, total 7 days (zusanli)

Non-EA

Proliferation

1. Brdu+ cells; 2. Nestin+ cells.

1. P < 0.05; 2. P < 0.05.

Li 2008 (29)

SD rats (male, 6/18)

220 ± 10 g

MCAO/2 h (ZL)

10% chloralhydrate (3 ml/Kg)

EA 30 min after reperfusion per day, with frequency of 2–15 Hz and current density of 1–5 mA, total 7 days (shuigou, baihui)

Non-EA

Proliferation

Brdu+ cells (7, 14, 30d)

P < 0.01 (7d)

You 2012 (30)

SD rats (male, 24/24)

450–500 g

Permanent MCAO

10% chloralhydrate (25 mg/100 g)

EA 20 min after surgery per day, with frequency of 2 Hz and current density of 1–2 mA (shousanli, waiguan, futu, zusanli)

Non-EA

Proliferation

1. NFS (Garcia, 1, 2, 3, 4w); 2. Infarct volume; 3. Nestin+ cells; 4. GAP-43+ cells.

1. P < 0.05 (2, 3d); 2. P < 0.05 (1, 2, 3w); 3. P < 0.05 (2, 3w); 4. P < 0.05 (2, 3w).

Mi 2010 (31)

SD rats (male, 90/90)

220–280 g

MCAO (ZL)

3.5% chloralhydrate (1 ml/100 g)

EA 20 min after surgery per day, with frequency of 10 Hz (baihui, quchi)

Non-EA

Proliferation

1. NFS (ZL, 6 h, 3, 7, 14, 21d); 2. Muscle testing; 3. GAP-43+ cells

1. P < 0.01 (21d), P > 0.05 (6 h, 3, 7, 14d); 2. P < 0.01 (14, 21d); 3. P < 0.01 (3, 7, 14d).

Bao 2007 (32)

Wistar rats (10/10)

300 ± 20 g

MCAO/ 1.5 h (ZL)

10% chloralhydrate (3 ml/Kg)

EA 30 min after reperfusion per day, with frequency of 5–30 Hz and current density of 2 V, total 28 days (baihui, dazhui, guanyuan, housanli)

Non-EA nor MA

Proliferation, differentiation

1. NFS (ZL, 1–28d); 2. Brdu+ cells (28d); 3. Nestin+ cells; 4. GFAP mRNA level; 5. Nestin mRNA level.

1. P < 0.05 (14, 17, 21, 24, 28d); 2. P < 0.01; 3. P < 0.01; 4. P < 0.05; 5. P < 0.01.

     

MA 30 min after reperfusion per day, with frequency of 5–30 Hz and current density of 2 V, total 28 days (baihui, dazhui, guanyuan, housanli)

Non-EA nor MA

  

1. P < 0.05 (14, 17, 21, 24, 28d); 2. P < 0.01; 3. P < 0.01; 4. P < 0.05; 5. P < 0.05.

Chen 2003 (33)

SD rats (male, 18/18)

200 ± 20 g

MCAO/2 h (ZL)

10% chloralhydrate (3 ml/Kg)

EA 30 min after reperfusion per day, with frequency of 4–16 Hz and current density of 3 mA (baihui, shangxing)

Non-EA;

Proliferation, migration.

1. NFS (ZL, 1–14d); 2. Infarct volume (4, 7, 14d); 3. Nestin+ cells; 4. Brdu+ cells; 5. PSA-NCAM.

1. P > 0.05; 2. P < 0.05 (7d), P > 0.05 (4, 14d); 3.P > 0.05; 4. P > 0.05; 5. P > 0.05.

Li 2004 (34)

SD rats (male, 40/40)

450–500 g

Permanent MCAO (Wahl)

10% chloralhydrate (300 mg/Kg)

EA 20 min after surgery per day, with frequency of 75 min−1 and current density of 1–2 mA (shousanli, waiguan, futu, zusanli)

Non-EA

Proliferation, migration, differentiation

1. NFS (Garcia, 1–14d); 2. Infarct size (1, 2, 3, 4w); 3. Brdu+ cells; 4. PSA-NCAM+ cells; 5. DCX+ cells; 6. Brdu/NeuN+ cells; 7. Brdu/GFAP+ cells

1. P < 0.05 (2, 3d); 2. P < 0.05 (2, 3w); 3. P < 0.05 (1, 2w); 4. P < 0.05 (1, 2, 3w); 5. P < 0.05; 6. P < 0.05 (1w); 7. P < 0.05 (3, 4w).

Zhang 2011 (35)

Wistar rats (female, 30/30)

200 ± 20 g

MCAO/1 h (ZL)

10% chloralhydrate (30 mg/Kg)

EA 20 min after reperfusion per day, with frequency of 2–100 Hz and current density of 2 mA

Non-EA

Proliferation, migration

1. NFS (ZL, 7, 14, 28d); 2. Brdu+ cells; 3. Brdu/ PSA-NCAM+ cells.

1. P < 0.05 (28d); 2. P < 0.01; 3. P < 0.01.

Zhao 2006 (36)

Wistar rats (male, 10/10)

320 ± 20 g

MCAO (ZL)

10% chloralhydrate (3 ml/Kg)

EA 15 min after surgery per day, with frequency of 5–30 Hz and current density of 0.8 mA, total 24 days. (baihui, fengfu)

Non-EA nor moxibustion

Proliferation, differentiation

1. NFS (ZL, 1–24d); 2. Nestin+ cells; 3. Brdu+ cells; 4. Nestin mRNA level; 5. GFAP mRNA level.

1. P < 0.05 (13, 16, 19, 22, 24d); 2. P < 0.01; 3. P < 0.01; 4. P < 0.05; 5. P < 0.05.

     

Moxibustion 15 min after surgery per day, total 24 days. (baihui, guanyuan, zusanli)

   

1.P < 0.05 (13, 16, 19, 22, 24d); 2. P < 0.01; 3. P < 0.01; 4. P < 0.01; 5. P < 0.05

Liu 2005 (37)

SD rats (male, 36/36)

250–280 g

Permanent MCAO

10 g/l pentobarbital sodium (50 mg/Kg)

EA 30 min after surgery per day, with frequency of 5–10 Hz. (baihui, dazhui)

Non-EA

Proliferation

1. NFS (Bederson, 3, 7, 14, 21d); 2. Nestin+ cells.

1. P < 0.05/0.01; 2. P < 0.05/0.01.

Yu 2010 (38)

Wistar rats (male, 25/25)

360 ± 20 g

MCAO (ZL)

10% chloralhydrate (35 mg/Kg)

EA 30 min after surgery per day (baihui, dazhui)

Non-EA

Proliferation

1. NFS (ZL, 1, 3, 7, 14, 21d); 2. Nestin+ cells.

1. P < 0.05/0.01; 2. P < 0.05/0.01 (3, 7, 14, 21d).

Wan 2010 (39)

SD rats (male, 48/48)

90–120 g

MCAO/2 h (ZL)

NR

EA 15 min after reperfusion per day, with frequency of 3 Hz and current density of 3 V, total 14 days. (baihui, dazhui)

Non-EA

Differentiation.

1. BWC (1, 7, 14, 28d); 2.GFAP+ cells.

1. P < 0.05 (1, 7d); 1. P < 0.05 (7, 14, 28d).

Zhao 2004 (40)

Wistar rats (male, 40/40)

250–300 g

MCAO/1 h (ZL)

3.5% chloralhydrate (10 ml/Kg)

EA 15 min after reperfusion per day, with frequency of 60/40 Hz and current density of 1.5 V, total 7 days. (hegu-L14)

Non-EA

Proliferation

1. Infarct volume (1d); 2. NFS (ZL, 1, 7, 14, 21, 28d); 3.Brdu+ cells; 4.Nestin+ cells.

1. P < 0.05; 2. P < 0.05; 3.P < 0.05 (7d); 4. P < 0.05 (7d).

Tao 2010 (41)

SD rats (male, 20/20)

250 ± 30 g

MCAO/2 h (ZL)

2% isoflurane

EA 30 min after reperfusion per day, with frequency of 1–20 Hz (quchi, zusanli)

Non-EA

Proliferation, differentiation

1. NFS (Garcia, 4, 7, 14, 21d); 2.Brdu+ cells; 3. Brdu/GFAP+ cells; 4. Brdu/NeuN+ cells.

1. P < 0.05 (7, 14, 21d); 2.P < 0.05 (7, 14d); 3. P < 0.05 (7, 14d); 4. P < 0.05 (21d).

Yang 2005 (42)

SD rats (male, 6/8)

220–250 g

MCAO/ 30 min (ZL)

10% chloralhydrate (360 mg/Kg)

EA 20 min after reperfusion per day, with frequency of 60/2 Hz and current density of 10 mA, total 13 days. (fengfu, jinsuo)

Non-EA

Proliferation, differentiation

1. Infarct volume; 2. Brdu+ cells; 3. Brdu/CRMP-4+ cells; 4. Brdu/MAP-2+ cells

1. P < 0.05; 2. P < 0.05; 3. P < 0.05; 4. P < 0.05.

Cheng 2009 (43)

SD rats (male, 12/12)

250–280 g

MCAO/2 h + PBS

10% chloralhydrate (350 mg/Kg)

EA 30 min after reperfusion per day, with frequency of 4 Hz and current density of 2 mA, total 3 days. (baihui, renzhong)

Non-EA + PBS

Proliferation

1. NFS (mNSS, 1, 7, 14, 21, 28d); 2. Infarct volume (28d); 3. Brdu+ cells (7, 28d).

1. P > 0.05; 2. P > 0.05; 3. P < 0.05.

Kim 2014 (44)

C57BL/6 mice (male, 6/6)

NR

MCAO/ 40 min (ZL)

isoflurane

EA 20 min from 5 day after reperfusion per day, with frequency of 2 Hz and output voltage of 2 V, total 10 days. (baihui GV20, dazhui GV14)

Non-EA

Proliferation, Differentiation

1. Rotarod test (40, 47d); 2. Morris water maze tests (44–46d); 3. Brdu+ cells (14d); 4. Brdu/Dcx+ cells (14d); 5. Brdu/NeuN+ cells (47d); 6. Brdu/ GFAP+ cells (47d).

1. P < 0.05/0.01; 2. P < 0.05; 3. P < 0.01; 4. P < 0.01; 5. P < 0.05; 6. P < 0.001.

  1. Note: TMS (total motor scores; CB: calbindin; MCAT: Middle CerebralArtery Trumbosis; PCNA proliferation cell nuclear antigen; BWC: Brain water content; NFS: Neural functional score; BMSC: bone marrow-derived mesenchymal stem cells; EA: electroaucpunture; MA: manual acupuncture; PSA-NCAM: polysialylated form of the neural cell adhesion molecule; Brdu: bromodeoxyuridine; GFAP: Glial fibrillary acidic protein; NR: no report.
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