Table 1.
Characteristics of studies included in the meta-analysis.
| References | Animals | Injury model | Animal number | Metformin source | Experimental groups | Control group | Outcome |
|---|---|---|---|---|---|---|---|
| Wu et al. (2021) | 108 female SD rats (220–250 g) | T9 vascular clip compression 15 g * 1 min | 36/36/36 | Sigma | A: SCI + metformin (50 mg/kg i.p., immediately post injury and once daily until sacrifice) | B: sham SCI + saline C: SCI + saline |
Behavioral: BBB scale, ICP, footprint analysis Histopathology: HE staining, LFB staining, Nissl staining, immunohistochemistry. IF Other: Western blot, PCR |
| Zhao et al. (2021) | 104 male SD rats (250–300 g) | T9-11 weight-drop impactor 10 g * 60 mm | 17/17/17/17; 12/12/12 | N/A | 1A: SCI + metformin (200 mg/kg i.p., immediately post injury and once daily until sacrifice); 2A: SCI + metformin (200 mg/kg i.p., immediately post injury and once daily until sacrifice); |
1B: sham SCI + saline 1C: sham SCI + metformin 1D: SCI + saline; 2B: SCI + saline 2C: SCI + metformin + SC-1 (10 μl intrathecal injection, 30 min piror to injury) |
Behavioral: BBB scale, ICP Histopathology: TTC staining, IF Other: Western blot, PCR, dot blot |
| Wang et al. (2020) | 70 female SD rats (220–250 g) | T9 vascular Clip compression 15 g* 1 min |
10/10/10; 10/10/10/10 | N/A | 1A: SCI + metformin (50 mg/kg i.p., immediately post injury and once daily for 14 d); 2A: SCI + metformin (50 mg/kg i.p., immediately post injury and once daily for 14 d) |
1B: sham SCI 1C: SCI + saline; 2B: sham SCI 2C: SCI + saline 2D: SCI + metformin + LY294002 (1.2 mg/kg i.p., immediately post injury and once daily for 14 d) |
Behavioral: BBB scale, footprint analysis Histopathology: HE staining, Nissl staining, TUNEL, IF Other: Western blot |
| Zhang et al. (2020) | 90 male SD rats (8–12 weeks, 180–220 g) | T9-10 weight-drop impactor 10 g * 30 mm | 18/18/18/18/18 | N/A | A: SCI + metformin (50 mg/kg i.p., once daily for 14 d post injury) | B: sham SCI + saline C: SCI + saline D: SCI + metformin + XAV939 (0.4 mg/kg i.p., once daily for 14 d post injury) E: SCI + MP (30 mg/kg i.p., immediately once daily for 14 d post injury) |
Behavioral: BBB scale Histopathology: HE staining, Nissl staining, TUNEL, IF Other: Western blot |
| Guo et al. (2019) | 36 female SD rats (250–300 g) | T9-T11 weight-drop impactor | 12/12/12 | MedChem Express | A: SCI + metformin (50 mg/kg i.p., immediately post injury and once daily for 7 d) | B: sham SCI C: SCI + saline |
Behavioral: BBB scale Histopathology: TUNEL, IF Other: Western blot, PCR |
| Afshari et al. (2018) | 48 male SD rats (240–260 g) | T9 aneurysmal Clip compression 110 g* 1 min |
8/8/8/8/8/8 | Sigma | A: SCI + metformin (10 mg/kg i.p., immediately post injury) B: SCI + metformin (50 mg/kg i.p., immediately post injury) C: SCI + metformin (100 mg/kg i.p., immediately post injury) |
D: sham SCI + saline E: SCI + saline F: SCI + minocycline (90 mg/kg i.p., immediately post injury and 45 mg/kg i.p., q12 h for 1 d) |
Behavioral: BBB scale, tail-flick latency, von Frey filaments test Histopathology: HE staining Other: Body weight, ELISA |
| Guo et al. (2018) | 60 female SD rats (200–240 g) | T9-10 weight-drop impactor 10 g * 50 mm | 20/20/20 | N/A | A: SCI + metformin (10 mg/kg i.p., once daily for 3 d post injury) | B: sham SCI + saline C: SCI + saline |
Behavioral: BBB scale Histopathology: Nissl staining, IF Other: Western blot |
| Wang et al. (2018) | 50 male SD rats (200–220 g) | T7-T10 bulldog clamp compression 30 g * 1 min | 10/10/10/10/10 | Boyun Biotechnology | A: SCI + metformin (50 mg/kg i.p., immediately and 24 h post injury) | B: SCI + saline C: SCI + compound C (20 mg/kg immediately and 24 h post injury) D: SCI + EPO (2,000 U/kg immediately and 24 h post injury) E: SCI + EPO + compound C |
Behavioral: BBB scale, ICP Histopathology: Nissl staining Other: Western blot |
| Zhang et al. (2017a) | 114 adult female SD rats (220–250 g) | T9 level vascular clip compression 30 g * 1 min | 18/18/18; 15/15/15/15 | MedChem Express | 1A: SCI + metformin (50 mg/kg i.p., immediately post injury and once daily for 28 d); 2A: SCI + metformin (50 mg/kg i.p., immediately post injury and once daily for 28 d) |
1B: Sham group 1C: SCI + saline; 2B: Sham group 2C: SCI + saline 2D: SCI + metformin + chloroquine (50 mg/kg i.p., immediately post injury and once daily for 28 d post injury) |
Behavioral: BBB scale, ICP Histopathology: HE staining, Nissl staining, IF Other: Western blot, transmission electron microscopy |
| Zhang et al. (2017b) | 105 adult female SD rats (220–250 g) | T9 level vascular clip compression 30 g * 1 min | 35/35/35 | MedChem Express | A: SCI + metformin (50 mg/kg i.p., immediately post injury and once daily for 14 d) | B: Sham group C: SCI + saline |
Behavioral: BBB scale Histopathology: HE staining, IF Other: Western blot, PCR, gelatin zymography, fluorimetric assay of MMP-9, myeloperoxidase activity, Evans blue, spinal cord oedema |
| Wang et al. (2016) | 48 adult female SD rats (180–220 g) | T9-10 weight-drop impactor 10 g * 25 mm | 14/6/14/14 | Sigma Aldrich | A: SCI + metformin (200 mg/kg i.p., once daily for 14 d prior to injury) B: SCI + metformin (100 mg/kg i.p., once daily for 3 d post injury) |
C: Sham group D: SCI + vehicle |
Behavioral: BBB scale Histopathology: HE staining, Nissl staining IF Other: Western blot |
| Lin et al. (2015) | 18 male Wistar rats | T8-9 level aneurysm Clip compression 55 g * 1 min |
6/6/6 | Tocris Bioscience | A: SCI + metformin (320 mg/kg i.v., once daily for 20 d after 1 week of SCI) | B: Sham group C: SCI + vehicle (DMSO diluted with saline) |
Behavioral: BBB scale, ICP, limb hanging test, pain test Other: Western blot |
BBB, Basso, Beattie, and Bresnahan; DMSO, dimethyl sulfoxide; ELISA, enzyme-linked immunosorbent assay; HE, hematoxylin-eosin; IF, immunofluorescence; ICP, inclined plane test; i.p., intraperitoneal injection; LFB, luxol fast blue; MMP-9, matrix metalloproteinase-9; MP, methylprednisolone; N/A, not available; PCR, Polymerase chain reaction; SD, Sprague-Dawley; SCI, spinal cord injury; TTC, 3,5-TriphenylTetrazolium chloride; TUNEL, Terminal dexynucleotidyl transferase mediated d UTP nick end labeling.