Protective Effect of Electroacupuncture on Neural Myelin Sheaths is Mediated via Promotion of Oligodendrocyte Proliferation and Inhibition of Oligodendrocyte Death After Compressed Spinal Cord Injury

Abstract

Electroacupuncture (EA) has been used worldwide to treat demyelinating diseases, but its therapeutic mechanism is poorly understood. In this study, a custom-designed model of compressed spinal cord injury (CSCI) was used to induce demyelination. Zusanli (ST36) and Taixi (KI3) acupoints of adult rats were stimulated by EA to demonstrate its protective effect. At 14 days after EA, both locomotor skills and ultrastructural features of myelin sheath were significantly improved. Phenotypes of proliferating cells were identified by double immunolabeling of 5-ethynyl-2'-deoxyuridine with antibodies to cell markers: NG2 [oligodendrocyte precursor cell (OPC) marker], 2',3'-cyclic-nucleotide 3'-phosphodiesterase (CNPase) (oligodendrocyte marker), and glial fibrillary acidic protein (GFAP) (astrocyte marker). EA enhanced the proliferation of OPCs and CNPase, as well as the differentiation of OPCs by promoting Olig2 (the basic helix-loop-helix protein) and attenuating Id2 (the inhibitor of DNA binding 2). EA could also improve myelin basic protein (MBP) and protect existing oligodendrocytes from apoptosis by inhibiting caspase-12 (a representative of endoplasmic reticulum stress) and cytochrome c (an apoptotic factor and hallmark of mitochondria). Therefore, our results indicate that the protective effect of EA on neural myelin sheaths is mediated via promotion of oligodendrocyte proliferation and inhibition of oligodendrocyte death after CSCI.

Electroacupuncture Promotes Remyelination after Cuprizone Treatment by Enhancing Myelin Debris Clearance

“…In a recent study, the research showed that EA can facilitate remyelination via promoting the proliferation of oligodendrocyte and inhibiting its death in SCI model (Huang et al, 2015), and here we report a new mechanism underlying the remyelinating effect of EA, which is by recruiting microglia into areas with demyelinating lesions to clear degraded myelin debris. However, further studies have to be conducted to understand the neural pathway and the precise molecular and cellular mechanisms of how EA regulate microglia recruitment, migration as well as polarization.…”

“…The results we obtained indicate that EA treatment enhances the expression of myelin-related components, which further support the results we obtained from behavioral tests. Together with previous research (Ding et al, 2013; Huang et al, 2015; Liu et al, 2015), we are inclined to conclude that EA is an effective healing method to facilitate remyelination in diseases with demyelination. However, we found a disparity in our RT-PCT results: the mRNA expression of MBP (also PLP1) at week 7 is not down-regulated whereas the expression of MBP detected by Western Blot and immuno-staining is reduced.…”

“…In addition, Laboratory studies based on experimental autoimmune encephalomyelitis (EAE) model, a classic animal model mainly mimicking the immunopathology of MS, also show that EA treatment inhibit the proliferation of encephalitogenic T cells, increase the secretion of ACTH and β-endorphin, and eventually ameliorate EAE (Park et al, 2004; Liu et al, 2013). A recent study indicates that EA promotes remyelination in compressed spinal cord injury (SCI) model by enhancing the proliferation of oligodendrocyte precursor cells (Huang et al, 2015). Additionally, EA promotes the differentiation of the transplanted bone marrow mesenchymal stem cells into oligodendrocyte-like cells in SCI model (Ding et al, 2013; Liu et al, 2015).…”

pEGFR promotes the neural function recovery after decompression of compressed spinal cord injury

“…Model groups: the CSCI model (Additional File 1) was constructed based on a previous method developed by our group [5,6,21]. The rats were fasted 24 hours prior to surgery, anesthetized by intraperitoneal injection of 3.5% chloral hydrate and subjected to continuous oxygen inhalation.…”

“…CSCI is usually caused by spinal tumors, spinal tuberculosis, vertebral fractures, epidural hematoma or other diseases [1][2][3][4]. Previous studies showed that demyelinating lesion is one of the important pathological changes of CSCI, while the apoptosis of OPCs is the main reason for demyelination after CSCI [5][6][7][8][9][10]. The nerve impulses of demyelinating nerve fibers become diffused during conduction, preventing the electrical conduction of axons and resulting in partial or complete inhibition of movement, sensation and sphincter functions below the level of injury [11][12][13][14].…”