Table 2.
Mechanism of acupuncture on the repair of spinal cord injury.
| Study | Acupuncture intervention | Control intervention | Effect indicators | Mechanism index |
|---|---|---|---|---|
| Neuroprotective effect of acupuncture | ||||
| [29] | EA (GV4; 2-100 Hz, 2.5 mA, 30 minutes) | EA (GV26) | Motor function↑, Basso-Beattie-Bresnahan (BBB) locomotor rating scale scores↑ | Hydroxyl radical concentration↓, lipid peroxidation↓ |
| [30] | EA (DU26, DU16; 2 Hz, 0.2 mA, 30 minutes) MA (DU26, DU16; 2 revolutions per second for 10 s, every 10 minutes, 30 minutes) |
No treatment | Neuronal function recovery↑, antioxidation↑, anti-inflammation↑, antiapoptosis effects↑ | IL-1β↓, IL-6↓, TNF-α↓ |
| [31] | EA (GV6, GV9; 60 Hz for 1.05 s and 2 Hz for 2.85 s, ≤1 mA, 20 minutes, once every other day, 4 weeks) | No treatment | BBB functional↑ | M1 (TNF-α↓, IL-1β↓, IL-6↓), M2 (IL-10↑, CD206↑), NT-3 expression↑, the polarization of M2 microglia/macrophages↑ |
| [32] | Acupuncture (GV26, GB34; two spins/second, 30 s, 30 minutes, once a day, 2 weeks) | Not received any acupuncture treatment | Functional recovery↑ | Caspase-3↓, p38 MAPK↓, resident microglia↓, TNF-α↓, IL-1β↓, IL-6↓, nitric oxide synthase↓, cycloxygenase-2↓, matrix metalloprotease-9↓ |
| [33] | Elongated needle (BL54, ST28, CV6, CV3; 20-40 times/min, 1.5-3 V, 15 minutes) | No acupuncture stimulation | Decrease spinal injury↓, cell apoptosis↓ | p-Akt and p-ERK1/2↑, Cyt c and caspase-3↓ |
| [34] | EA (ST36, KI3; 60 Hz for 1.05 s and 2 Hz for 2.85 s, ≤2 mA, 20 minutes) | No electrical stimulation | Locomotor skills↑, ultrastructural features of the myelin sheath↑ | Caspase-12↑, Cyt c↑, oligodendrocyte proliferation↑, oligodendrocyte death↓ |
| [35] | EA (GV6, GV9; 60 Hz, 20 minutes) | No acupuncture stimulation | Functional recovery↑, tissue loss and neuronal apoptosis↓ | Proapoptotic proteins (cleaved caspase-3/9↓ and cleaved PARP↓), antiapoptotic protein Bcl-2↑, miR-214↑ |
| [36] | Elongated needle (BL54, ST28; 20–40beats/min, 1.5–3 V, 15 minutes) | Control group | Cell apoptosis↓ | FAS → caspase-3 cascade↓ |
| [37] | Elongated needle therapy (BL54, ST28; 2 Hz, 1-3 mA, 15 minutes) | Not received acupuncture treatment | BBB locomotor scale↑ | PI3K/Akt and MAPK/ERK signaling pathways↑, Bax protein↓, Bcl-2↑, mitochondrial apoptosis pathway↓ |
| [38] | EA (BL54, ST28, CV6, CV3; 20 Hz/40 Hz, 15 minutes) | Elongated needle EA | Promote repair↑ | PI3K/Akt↑, ERK1/2↑, Cyt c↓, caspase-3↓ |
| [29] | EA (GV4; 2.5 mA, 2-100 Hz, 30 minutes) | EA (GV26) | Motor function↑, BBB locomotor scale↑ | Hydroxyl radical concentration↓, lipid peroxidation↓ |
|
| ||||
| Acupuncture modulates neural plasticity and promotes neural regeneration | ||||
| Wnt signaling pathway | ||||
| [39] | EA (GV14, GV4; 2 Hz, 1 mA, 20 minutes) | Not received EA treatment | Hindlimb motor functions↑, neuroprotective effects↑, proliferation and differentiation of neural stem cells↑ | Wnt/β-catenin signaling pathway↑, proliferation and differentiation of neural stem cells↑ |
| [40] | Fire needle acupuncture (T7, T8, T11, T12; 1/3 s, 3-5 mm, once a day) | Not treated by fire needle acupuncture | Lower limb locomotor function↑ | Wnt/β-catenin↑, ERK↓, nestin↑, NSE↑, Gal-C↑, GFAP↓; Wnt-3a↑, GSK3β↑, β-catenin↑, ngn1↑, ERK1/2↓, cyclin D1 gene and protein↓ |
| Notch signaling pathway | ||||
| [42] | EA (GV14, GV4; 2 Hz, 2 V, 30 minutes, once a day) | Without any treatment | Morphological recovery↑ | Notch signaling pathway↓, promoting the proliferation of endogenous neural stem cells↑ |
| [43] | EA (GB30, Ex-B05; 100 Hz/2 s and 2 Hz/2 s, 3 mA, 5 mm) | Not received EA treatment | Spontaneous regeneration↑, remyelination↑, recovery of function↑ | BrdU(+)/NG2(+) cells↑, the proliferation of endogenous neural stem cells and oligodendrocytes↑ |
| Rho/ROCK signaling | ||||
| [46] | EA (DU14, DU4, SP6, GB30, ST36, BL60; 4 Hz, 30 minutes, once a day, 7 days) | No acupuncture stimulation | Tissue repair and neurological functional recovery↑, BBB locomotor scale and inclined plane test scores↑ | Neuronal apoptosis↓, decreases RhoA↓, Nogo-A mRNA↓ |
| [47] | EA (GV3, GV14, ST36, BL32; 100 Hz for 1.5 ms and 2 Hz for 1.5 ms) | Blocking agent Y27632 | Spinal cord tissue morphology↑, BBB score of lower limb movement function↑ | Rho/ROCK signaling pathway↓, axonal growth and inflammatory reaction↓ |
| [48] | EA (Ex-B2; 100 Hz, 30 minutes, once daily for 14 days and 28 days) | ROCK inhibitor groups | Hindlimb locomotor function↑ | RhoA/ROCK signaling pathway↓ (RhoA↓, ROCK II↓, MLC proteins↓) |
| [49] | EA (GV3, GV14, ST36, BL32; 100 Hz for 1.5 ms and 2 Hz for 1.5 ms, 2 V, 20 minutes,14 days) | Blocking agent Y27632 EA+Y | Lower limb movement function↑ | Nogo/NgR and Rho/ROCK signaling pathway↓ (mRNA and protein expression of Nogo-A↓, NgR↓, LINGO-1↓, RhoA and ROCK II↓) |
| [57] | EA (GV3, GV14, ST36, BL32; 2 Hz, 2 V, 20 minutes, 14 days) | Monosialoganglioside treatment | Hindlimb motor functions↑ | Rho-A and Rho-associated kinase II (ROCK II)↓, Rho/ROCK signaling pathway↓ |
| Neurotrophic factors | ||||
| [58] | EA (ST36, GB39, ST32, SP6; 2 Hz, 98 pulses per minute, 15 minutes, ST36 and GB39, first day, ST32 and SP6, second day, each pair of acupoints was stimulated on alternate days) | Not received EA treatment | Sensory functional↑ | CNTF↓, p75-like apoptosis-(death domain protein↓, IGF-1↓, transforming growth factor-beta 2↓, FGF-4↓) |
| [53] | EA (ST36, GB39, ST32, SP6; alternating stimulus, 98 Hz, 30 minutes, the stimulating electrodes were changed and their polarity reversed after 15 minutes) | Not received EA treatment | Hindlimb locomotor and sensory functions↑ | CNTF↑, FGF-2↑, TrkB mRNA↑; NGF, PDGF↓, TGF-β1↓, IGF-1↓, TrkA↓, TrkC mRNA↓ |
| [50] | EA (GV1; 2 Hz, 2 mA, 20 minutes, once a day) | Not received EA treatment | BBB↑ | NGF↑, BDNF↑ |
| [59] | EA (ST36, GB39, ST32, SP6; 75 cycles/minute, 40-50 μA, 30 minutes, once a day) | No treatment | BBB locomotor rating scale scores↑, motor neuron function↑ | AChE activity↑, GDNF↑ |
| [51] | EA (GV14, GV4; 2 Hz, 1 mA, 20 minutes) | No treatment | Motor function↑, neuronal function↑ | NT-3↑ |
| [52] | EA-2 group (GV20, GV16, GV14, GV4; GV14 and GV4, 2 Hz, 0.2 mA, 30 minutes, once every 2 days, 6 weeks) | EA-1 group | BBB locomotor rating scale scores↑, locomotor function↑ | BDNF↑, NT-3↑ |
| [54] | EA (GV14, GV4, GV7, GV5; alternating stimulus, 2 Hz, 10 minutes, 6 days EA-1 day interval-6 days EA) | No treatment | Movement function↑ | BDNF↑, CREB↑ |
| [38] | EA (BL54, ST28, CV6, CV3; 20 Hz/40 Hz) | Only performed a laminectomy | Promote repair↑ | PI3K/Akt↑, ERK1/2↑, cytochrome c↓, caspase-3↓ |
| [60] | EA (GV4, GV14; GV9, GV6; 2 Hz, 20 minutes) | Not received EA treatment | Hindlimb locomotor↑ and sensory functions↑ | IGF-1↓, FGF-2↓, CNTF↓, PDGF↓, TGF-β1↓, TrkA↓, TrkB↓, TrkC↓, NTFs↑ |
| [55] | EA (Ex-B2, 2 Hz; 3, 7, and 14 days) | Not received EA treatment | BBB locomotor scoring↑, hindlimb locomotor function↑ | EGFR↓, GFAP↓, nerve axon regeneration↑ |
| [56] | EA (Ex-B2, 2/100 Hz, 0.2 mA, 15 minutes) | Not received EA treatment | Locomotor function↑ | L1↑, GFAP↑, (early phase)-(GFAP)↓, (later stages), nestin↑ |
| [58] | EA (ST36, GB39, ST32, SP6; alternating stimulus, 2 Hz, 98 pulses/minute, 15 minutes, after the third day, stimulate every other day) | Not received EA treatment | Sensory functional↑ | CNTF↓, p75-like apoptosis-(death domain protein↓, IGF-1↓, transforming growth factor-beta 2↓, FGF-4↓) |
Abbreviation: GV4: Mingmen; GV26: Shuigou; BBB: Basso-Beattie-Bresnahan; DU16: Fengfu; IL-1β: interleukin-1β; IL-6: interleukin-6; TNF-α: tumor necrosis factor-α; GV6: Jizhong; GV9: Zhiyang; NT-3: neurotrophin-3; GB34: Yanglingquan; MAPK: mitogen-activated protein kinase; BL54: Zhibian; ST28: Shuidao; CV6: Qihai; CV3: Zhongji; Cyt c: cytochrome c; ST36: Zusanli; KI3: Taixi; GV4: Mingmen; GV14: Dazhui; SCI: spinal cord injury; ERK: extracellular signal-regulated kinase; GSK3β: glycogen synthase kinase 3β; GB30: Huantiao; Ex-B05: Huatuojiaji; BL32: Ciliao; ST32: Futu; GV1: Changqiang; NGF: nerve growth factor; BDNF: brain-derived neurotrophic factor; AChE: acetylcholinesterase; GDNF: glial cell line-derived neurotrophic factor; GV20: Baihui; GV7: Zhongshu; GV5: Xuanshu; Ex-B2: Jiaji; CREB: cAMP response element-binding; NTFs: neurotrophic factors; EGFR: epidermal growth factor receptor; GFAP: glial fibrillary acidic protein.