Review Article

Effects and Mechanisms of Acupuncture Combined with Mesenchymal Stem Cell Transplantation on Neural Recovery after Spinal Cord Injury: Progress and Prospects

Table 2

Mechanism of acupuncture on the repair of spinal cord injury.

StudyAcupuncture interventionControl interventionEffect indicatorsMechanism 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 treatmentNeuronal 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 treatmentBBB 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 treatmentFunctional 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 stimulationDecrease 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 stimulationLocomotor 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 stimulationFunctional 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 groupCell apoptosis↓FAS → caspase-3 cascade↓
[37]Elongated needle therapy (BL54, ST28; 2 Hz, 1-3 mA, 15 minutes)Not received acupuncture treatmentBBB 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 EAPromote 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 treatmentHindlimb 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 acupunctureLower 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 treatmentMorphological 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 treatmentSpontaneous 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 stimulationTissue 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 Y27632Spinal 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 groupsHindlimb 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+YLower 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 treatmentHindlimb 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 treatmentSensory 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 treatmentHindlimb 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 treatmentBBB↑NGF↑, BDNF↑
[59]EA (ST36, GB39, ST32, SP6; 75 cycles/minute, 40-50 μA, 30 minutes, once a day)No treatmentBBB locomotor rating scale scores↑, motor neuron function↑AChE activity↑, GDNF↑
[51]EA (GV14, GV4; 2 Hz, 1 mA, 20 minutes)No treatmentMotor 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 groupBBB 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 treatmentMovement function↑BDNF↑, CREB↑
[38]EA (BL54, ST28, CV6, CV3; 20 Hz/40 Hz)Only performed a laminectomyPromote repair↑PI3K/Akt↑, ERK1/2↑, cytochrome c↓, caspase-3↓
[60]EA (GV4, GV14; GV9, GV6; 2 Hz, 20 minutes)Not received EA treatmentHindlimb 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 treatmentBBB 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 treatmentLocomotor 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 treatmentSensory 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.