A comparison of adenosine A2A agonism and methylprednisolone in attenuating neuronal damage and improving functional outcome after experimental traumatic spinal cord injury in rabbits

Object Steroid agents remain the lone pharmacological treatment in widespread use for acute spinal cord injury (SCI), although their utility remains in dispute in the neurotrauma literature. Adenosine A2A receptor activation with ATL-146e, a selective A2A agonist, has shown potential benefit in treating SCI; however, it has not been compared with the gold standard, methylprednisolone. The authors of this study evaluated ATL-146e and methylprednisolone for their ability to preserve neuronal viability and motor function in experimental SCI. Methods New Zealand White rabbits sustained SCI or sham injury via the Allen weight-drop technique. Ten minutes postinjury, animals received ATL-146e (ATL group, 0.06 μg/kg/min intravenously for 3 hours), methylprednisolone (steroid group, 30 mg/kg intravenously), or saline (trauma control group). Hindlimb motor function was recorded every 12 hours using the Tarlov motor grading scale (0, paralysis–5, normal hop). At 48 hours, fixed spinal cord tissue was evaluated for neuronal viability. Hindlimb motor function in animals treated with ATL-146e was equivalent to that of sham-injured animals and was significantly better than that of trauma control animals at all time points and that of steroid-treated animals at 12 hours (p = 0.05). Motor function in steroid-treated animals was worse than in those given ATL-146e and better than that of trauma control animals at later time points, but was not statistically significant (both p > 0.05). Neuronal viability (measured in neurons/hpf) was significantly higher in both treatment groups compared with the trauma control group (12.1 ± 1.4 neurons/hpf for the ATL and 13.3 ± 1.4 neurons/hpf for the steroid group compared with 7.5 ± 1.5 neurons/hpf for the trauma control group; both p < 0.04). Neuronal viability did not differ among ATL-146e–treated, steroid-treated, and sham-injured groups. Conclusions The use of ATL-146e is at least as effective as methylprednisolone in preserving function and is equivalent to methylprednisolone in preserving the structure of spinal cord tissue after blunt SCI. Adenosine A2A receptor activation may be an effective treatment for acute SCI while avoiding the adverse effects of steroid agents.

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Neuroprotective effects of Nigella sativa on experimental spinal cord injury in rats

Human & Experimental Toxicology ◽

10.1191/0960327106ht608oa ◽

2006 ◽

Vol 25 (3) ◽

pp. 127-133 ◽

Cited By ~ 54

Author(s):

M Kanter ◽

O Coskun ◽

M Kalayc ◽

S Buyukbas ◽

F Cagavi

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

Nigella Sativa ◽

Protein Carbonyl ◽

Control Group ◽

Spinal Cord Tissue ◽

Neuroprotective Effects ◽

Tissue Samples ◽

Experimental Spinal Cord Injury ◽

Cord Injury

The aim of this study was to investigate the possible beneficial effects of Nigella sativa (NS) in comparison to methylprednisolone on experimental spinal cord injury (SCI) in rats. SCI was performed by placing an aneurysm clip extradurally at the level of T11-12. Rats were neurologically tested over 24 h after trauma and spinal cord tissue samples were harvested for both biochemical and histopathological evaluation. The neurological scores of rats were not found to be different in SCI groups. SCI significantly increased the spinal cord tissue malondialdehyde (MDA) and protein carbonyl (PC) levels, however SCI decreased superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (CAT) enzyme activities compared to the control. Methylprednisolone and NS treatment decreased tissue MDA and PC levels and prevented inhibition of SOD, GSH-Px and CAT enzymes in the tissues. The most significant results were obtained when NS was given. In SCI and placebo groups, the neurons of spinal cord tissue became extensively dark and degenerated with picnotic nuclei. The morphology of neurons in methylprednisolone and NS-treated groups were well protected, however, not as well as the neurons of the control group. The number of neurons in the spinal cord tissue of the SCI and placebo groups was significantly less than the control, laminectomy, methylprednisolone and NS-treated groups. In conclusion, NS treatment might be beneficial in spinal cord tissue damage, and therefore shows potential for clinical implications.

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Rapamycin Preserves Neural Tissue, Promotes Schwann Cell Myelination and Reduces Glial Scar Formation After Hemi-Contusion Spinal Cord Injury in Mice

Frontiers in Molecular Neuroscience ◽

10.3389/fnmol.2020.574041 ◽

2021 ◽

Vol 13 ◽

Author(s):

Junhao Liu ◽

Ruoyao Li ◽

Zucheng Huang ◽

Junyu Lin ◽

Wei Ji ◽

...

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

White Matter ◽

Schwann Cell ◽

Motor Function ◽

Neural Tissue ◽

Glial Scar ◽

Vehicle Group ◽

Spinal Cord Tissue ◽

Cord Injury

Protecting white matter is one of the key treatment strategies for spinal cord injury (SCI), including alleviation of myelin loss and promotion of remyelination. Rapamycin has been shown neuroprotective effects against SCI and cardiotoxic effects while enhancing autophagy. However, specific neuroprotection of rapamycin for the white matter after cervical SCI has not been reported. Therefore, we aim to evaluate the role of rapamycin in neuroprotection after hemi-contusion SCI in mice. Forty-six 8-week-old mice were randomly assigned into the rapamycin group (n = 16), vehicle group (n = 16), and sham group (n = 10). All mice of the rapamycin and vehicle groups received a unilateral contusion with 1.2-mm displacement at C5 followed by daily intraperitoneal injection of rapamycin or dimethyl sulfoxide solution (1.5 mg⋅kg–1⋅day–1). The behavioral assessment was conducted before the injury, 3 days and every 2 weeks post-injury (WPI). The autophagy-related proteins, the area of spared white matter, the number of oligodendrocytes (OLs) and axons were evaluated at 12 WPI, as well as the glial scar and the myelin sheaths formed by Schwann cells at the epicenter. The 1.2 mm contusion led to a consistent moderate–severe SCI in terms of motor function and tissue damage. Rapamycin administration promoted autophagy in spinal cord tissue after injury and reduced the glial scar at the epicenter. Additionally, rapamycin increased the number of OLs and improved motor function significantly than in the vehicle group. Furthermore, the rapamycin injection resulted in an increase of Schwann cell-mediated remyelination and weight loss. Our results suggest that rapamycin can enhance autophagy, promote Schwann cell myelination and motor function recovery by preserved neural tissue, and reduce glial scar after hemi-contusive cervical SCI, indicating a potential strategy for SCI treatment.

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Mmu-miR-27a-5p Promotes the Polarization of Macrophages to the M2 Phenotype at the Site of Spinal Cord Injury in Mice

10.21203/rs.3.rs-111721/v1 ◽

2021 ◽

Author(s):

Mingkun Yang ◽

Xiaoqian Dang ◽

Xu Zhang ◽

Chuan Liu ◽

Min He

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

Motor Function ◽

Macrophage Polarization ◽

Spinal Cord Tissue ◽

Injured Spinal Cord ◽

Arginase 1 ◽

Tnf Α ◽

Cord Injury ◽

M2 Phenotype

Abstract BackgroundTo investigate the effect of mmu-miR-27a-5p on macrophage polarization in the injured spinal cord and the recovery of motor function after spinal cord injury (SCI) in mice.MethodsA total of 160 specific-pathogen-free male mice were randomly divided into sham, model, mmu-miR-27a-5p, mmu-miR-27a-5p-negative control (NC) groups, with 40 mice in each group. Hindlimb motor function was assessed using the Basso Mouse scale (BMS) before injury and at 1, 3, 7, and 14 days after surgery. Spinal cord tissue samples were obtained at 1, 3, 7, and 14 days after surgery, and macrophage polarization types were detected by using western blot analysis, immunofluorescence, flow cytometry and RT-qPCR.ResultsThe BMS score in the mmu-miR-27a-5p group was significantly higher than that in the model and mmu-miR-27a-5p-NC groups at 7 and 14 days after SCI (X2=26.45-57.62, P<0.05). No significant changes in the expression of M1 markers IL-1β, TNF-α and M2 markers IL-10, Arginase-1 at each time point in the sham group (P=0.96). The expression of IL-1β and TNF-α was significantly lower, while the expression of IL-10 and Arginase-1 were significantly higher in the mmu-miR-27a-5p group as compared to the model and mmu-miR-27a-5p-NC groups at 7 and 14 days after SCI (P<0.05).ConclusionAdministration of mmu-miR-27a-5p can promote the polarization of macrophages to the M2 phenotype in the injured spinal cord, and improve motor function recovery within 14 days after SCI in mice.

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Transplantation of rat cranial bone-derived mesenchymal stem cells promotes functional recovery in rats with spinal cord injury

Scientific Reports ◽

10.1038/s41598-021-01490-1 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Yuyo Maeda ◽

Takashi Otsuka ◽

Masaaki Takeda ◽

Takahito Okazaki ◽

Kiyoharu Shimizu ◽

...

Keyword(s):

Spinal Cord ◽

Stem Cells ◽

Spinal Cord Injury ◽

Mesenchymal Stem Cells ◽

Motor Function ◽

Cranial Bone ◽

Transcranial Electrical Stimulation ◽

Spinal Cord Tissue ◽

Cell Based Therapy ◽

Cord Injury

AbstractCell-based therapy using mesenchymal stem cells (MSCs) is a novel treatment strategy for spinal cord injury (SCI). MSCs can be isolated from various tissues, and their characteristics vary based on the source. However, reports demonstrating the effect of transplanted rat cranial bone-derived MSCs (rcMSCs) on rat SCI models are lacking. In this study, we determined the effect of transplanting rcMSCs in rat SCI models. MSCs were established from collected bone marrow and cranial bones. SCI rats were established using the weight-drop method and transplanted intravenously with MSCs at 24 h post SCI. The recovery of motor function and hindlimb electrophysiology was evaluated 4 weeks post transplantation. Electrophysiological recovery was evaluated by recording the transcranial electrical stimulation motor-evoked potentials. Tissue repair after SCI was assessed by calculating the cavity ratio. The expression of genes involved in the inflammatory response and cell death in the spinal cord tissue was assessed by real-time polymerase chain reaction. The transplantation of rcMSCs improved motor function and electrophysiology recovery, and reduced cavity ratio. The expression of proinflammatory cytokines was suppressed in the spinal cord tissues of the rats that received rcMSCs. These results demonstrate the efficacy of rcMSCs as cell-based therapy for SCI.

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Post–spinal cord injury astrocyte-mediated functional recovery in rats after intraspinal injection of the recombinant adenoviral vectors Ad5-VEGF and Ad5-ANG

Journal of Neurosurgery Spine ◽

10.3171/2016.9.spine15959 ◽

2017 ◽

Vol 27 (1) ◽

pp. 105-115 ◽

Cited By ~ 10

Author(s):

Tatyana Povysheva ◽

Maksim Shmarov ◽

Denis Logunov ◽

Boris Naroditsky ◽

Ilya Shulman ◽

...

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

Motor Function ◽

Fold Increase ◽

Adenoviral Vectors ◽

Control Group ◽

Cord Injury ◽

Lateral Sclerosis ◽

Recovery Of Motor Function ◽

Intraspinal Injection

OBJECTIVEThe most actively explored therapeutic strategy for overcoming spinal cord injury (SCI) is the delivery of genes encoding molecules that stimulate regeneration. In a mouse model of amyotrophic lateral sclerosis and in preliminary clinical trials in patients with amyotrophic lateral sclerosis, the combined administration of recombinant adenoviral vectors (Ad5-VEGF+Ad5-ANG) encoding the neurotrophic/angiogenic factors vascular endothelial growth factor (VEGF) and angiogenin (ANG) was found to slow the development of neurological deficits. These results suggest that there may be positive effects of this combination of genes in posttraumatic spinal cord regeneration. The objective of the present study was to determine the effects of Ad5-VEGF+Ad5-ANG combination therapy on motor function recovery and reactivity of astrocytes in a rat model of SCI.METHODSSpinal cord injury was induced in adult Wistar rats by the weight-drop method. Rats (n = 51) were divided into 2 groups: the experimental group (Ad5-VEGF+Ad5-ANG) and the control group (Ad5-GFP [green fluorescent protein]). Recovery of motor function was assessed using the Basso, Beattie, and Bresnahan scale. The duration and intensity of infectivity and gene expression from the injected vectors were assessed by immunofluorescent detection of GFP. Reactivity of glial cells was assessed by changes in the number of immunopositive cells expressing glial fibrillary acidic protein (GFAP), S100β, aquaporin 4 (AQP4), oligodendrocyte transcription factor 2, and chondroitin sulfate proteoglycan 4. The level of S100β mRNA expression in the spinal cord was estimated by real-time polymerase chain reaction.RESULTSPartial recovery of motor function was observed 30 days after surgery in both groups. However, Basso, Beattie, and Bresnahan scores were 35.9% higher in the Ad5-VEGF+Ad5-ANG group compared with the control group. Specific GFP signal was observed at distances of up to 5 mm in the rostral and caudal directions from the points of injection. A 1.5 to 2.0–fold increase in the number of GFAP+, S100β+, and AQP4+ cells was observed in the white and gray matter at a distance of up to 5 mm from the center of the lesion site in the caudal and rostral directions. At 30 days after injury, a 2-fold increase in S100β transcripts was observed in the Ad5-VEGF+Ad5-ANG group compared with the control group.CONCLUSIONSIntraspinal injection of recombinant adenoviral vectors encoding VEGF and ANG stimulates functional recovery after traumatic SCI. The increased number of S100β+ astrocytes induced by this approach may be a beneficial factor for maintaining the survival and function of neurons. Therefore, gene therapy with Ad5-VEGF+Ad5-ANG vectors is an effective therapeutic method for SCI treatment.

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Assessment of neuroprotective role of PPAR-gamma agonist in spinal cord injury as possible therapeutic agents

Journal of Experimental and Applied Animal Sciences ◽

10.20454/jeaas.2018.1387 ◽

2018 ◽

Vol 2 (3) ◽

pp. 251-259

Author(s):

Zahra Jahanbakhsh ◽

Hassan Ghoshooni ◽

Mohammad Taghi Mohammadi

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

Oxidative Damage ◽

Motor Function ◽

Ppar Gamma ◽

Control Group ◽

Injured Spinal Cord ◽

Histopathological Changes ◽

Cord Injury ◽

Ppar Gamma Agonist

It has been reported that peroxisome proliferator-activated receptor (PPAR)-gamma agonist, pioglitazone, has several beneficial roles in many pathological states of nervous tissues. Then in the present study, we aimed to examine the neuroprotective actions of pioglitazone (PPAR-gamma agonist) on motor function, histopathological changes and oxidative damage during spinal cord injury (SCI) in rats. Twenty-four male Wistar rats were randomly divided into three groups as follows; sham, control injury and pioglitazone-treated injured groups. SCI was performed according to the Ping-Weight Drop (contusion) model in rat. The animals received pioglitazone (3 mg/kg) intraperitoneally at times of 15 min after injury and then each 12 hours for seven days. At day seven after SCI, the malondialdehyde and glutathione levels were assessed using biochemical techniques. Histopathological alterations in injured spinal cord and motor function recovery were also assessed after six weeks. Induction of SCI in control group significantly increased the malondialdehyde levels (56%, P=0.002) and decreased the content of glutathione (39±4 nMol/mL) compared to control group (49±6 nMol/mL). Pioglitazone in treated injured rats significantly decreased the malondialdehyde levels (37%, P=0.018) but not glutathione levels (42±1 nMol/mL) compared to sham group. In addition, pioglitazone noticeably improved the histopathological changes of injured spinal cord but not motor function. Our findings revealed that pioglitazone decreases histopathological changes and oxidative damage of injured spinal cord. However, it is suggested that pioglitazone must be applied at higher doses for improving motor function during SCI.

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Jia-Ji Electro-Acupuncture Improves Locomotor Function With Spinal Cord Injury by Regulation of Autophagy Flux and Inhibition of Necroptosis

Frontiers in Neuroscience ◽

10.3389/fnins.2020.616864 ◽

2021 ◽

Vol 14 ◽

Author(s):

Yin Hongna ◽

Tian Hongzhao ◽

Li Quan ◽

Feng Delin ◽

Liu Guijun ◽

...

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

Motor Function ◽

Acupuncture Treatment ◽

Spinal Cord Tissue ◽

Autophagy Flux ◽

Nissl Staining ◽

Microscopy Imaging ◽

Locomotor Function ◽

Cord Injury

Jia-Ji electro-acupuncture (EA) has been widely applied in clinic to exhibit curative effects on spinal cord injury (SCI). However, its underlying mechanisms leading to improvement of motor function after SCI remain unclear. Allen’s method was made by NYU Impactor M-III equipment to create the SCI rats model. Rats were randomly divided into four groups: Sham (only laminectomy), Model (SCI group), EA (SCI + Jia-Ji EA treatment), EA + CQ (SCI + Jia-Ji EA treatment + inhibitor chloroquine). Basso-Beattie-Bresnahan assessment showed improvement of hind limb motor function after Jia-Ji electro-acupuncture treatment. Histological change of injured spinal cord tissue was alleviated after treatment, observed by hematoxylin-eosin and Nissl staining. The mRNA and protein expression levels of RIPK1, RIPK3 and MLKL were decreased in EA group. Besides, the increased expression of LC3 and reduced expression of P62 after treatment compared with Model group, confirmed that Jia-Ji electro-acupuncture could enhance the autophagy flux. Electron microscopy imaging showed increasing the number of lysosomes, autophagosomes, and autolysosomes after Jia-Ji electro-acupuncture treatment. Furthermore, inhibition of lysosome function with CQ led to partly eliminate the effect of EA on reducing necroptosis. These data make the case that Jia-Ji electro-acupuncture treatment may improve locomotor function by promoting autophagy flux and inhibiting necroptosis.

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Effect of fetal cerebellar tissue transplantation on the restoration of hind limb locomotor function in rats with spinal cord injury

Cell and Organ Transplantology ◽

10.22494/cot.v4i2.57 ◽

2016 ◽

Vol 4 (2) ◽

pp. 175-180

Author(s):

V. Medvediev ◽

Yu. Senchyk ◽

N. Draguntsova ◽

S. Dychko ◽

V. Tsymbaliuk

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

Motor Function ◽

Hind Limb ◽

Tissue Transplantation ◽

Control Group ◽

Function Recovery ◽

Cord Injury ◽

Cerebellar Tissue ◽

Positive Effect

Fetal cerebellar tissue contains the largest number of neurogenic progenitors committed on the differentiation into glutamatergic neurons that can be used in the development of promising new treatment for spinal cord injuries.To evaluate the effect of fetal cerebellar tissue transplantation (FСTT) on the restoration of motor function after spinal cord injury in experiment.Materials and methods. Animals: inbred albino Wistar rats (5.5 months males, weighting 300 grams); main experimental groups: 1 – spinal cord injury + transplantation of a fragment of fetal (E18) rat cerebellum (n = 15), 2 – spinal cord injury only (n = 40). Model of an injury – left-side spinal cord hemisection at Т11; monitoring of the ipsilateral hind limb function (IHLF) – the Вasso-Вeattie-Вresnahan (BBB) scale.Results. FСTT normalizes the distribution of IHLF values, distorts the dynamics of the motor function recovery, transforming it from a progressive (in a control group) to the constant with variation within 3-3.6 points BBB during the experiment. FСTT causes early temporary positive effect on the functional state of the motor system, probably provided by mediator-dependent, neuroprotective, proangiogenic effect and remyelination. In our view, the gradual depletion of the FСTT positive effect due to resorption of the graft within the first 2 months is compensated by autoregenerative neoplastic process that is typical for the control group and by autoimmune utilization of myelin-associated inhibitors of axonal growth in the zone of injury that causes stability of the IHLF value during the observation period.Conclusion. Transplantation of fetal cerebellar tissue causes a short-term positive effect on the motor function recovery limited by the 1st month of the traumatic process. Evaluation of such type of neurotransplantation effectiveness requires taking into account the dynamics of the spasticity and chronic pain.

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Anti-inflammatory and antioxidative effects of genistein in a model of spinal cord injury in rats

Asian Biomedicine ◽

10.2478/abm-2021-0029 ◽

2021 ◽

Vol 15 (5) ◽

pp. 233-243

Author(s):

Ercan Bal ◽

Şahin Hanalioğlu ◽

Aydın Sinan Apaydın ◽

Ceylan Bal ◽

Almila Şenat ◽

...

Keyword(s):

Oxidative Stress ◽

Spinal Cord ◽

Spinal Cord Injury ◽

Functional Score ◽

Control Group ◽

Spinal Cord Tissue ◽

Total Thiol ◽

Secondary Damage ◽

Cord Injury ◽

Anti Inflammatory

Abstract Background Neurological damage from spinal cord injury (SCI) is a result of primary mechanical injury and secondary damage from oxidative stress and neuroinflammation. Although genistein has been shown to have potent antioxidant and anti-inflammatory effects in studies of brain injury, its effect on secondary damage in SCI has remained unknown. Objective To determine effects of genistein in a model of SCI in rats. Methods We divided 21 rats evenly into 3 groups, a control group, in which only a laminectomy was performed; a trauma group in which SCI was induced; and a genistein group in which genistein was administered subcutaneously after SCI. The rats were assessed using a Basso–Beattie and Bresnahan functional score at the 12th hour and on the 1st, 3rd, 5th, and 7th days. Biochemical analyses were conducted at the same time points to determine the serum levels of catalase, ischemia-modified albumin (IMA), disulfide (SS), total thiol (TT), native thiol (NT), disulfide/total thiol (SS/TT), and native thiol/total thiol (NT/TT). Total oxidant and antioxidant capacity, and oxidative stress index were determined in spinal cord tissue obtained on the 7th day together with immunohistochemistry for cyclooxygenase-2 levels. Result Catalase activity on the 7th day was significantly (P = 0.001) higher in the genistein-treated rats than in other groups, and IMA levels became stable earlier (3rd day) in the genistein group. SS values were significantly (P = 0.004) lower in the genistein group. NT/TT ratio were significantly (P = 0.049) higher in the genistein-treated rats on the 7th day. Conclusion Genistein has antioxidant, anti-inflammatory, and protective effects in a model of SCI in rats and warrants further study.

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Mettl14-mediated m6A modification modulates neuron apoptosis during the repair of spinal cord injury by regulating the transformation from pri‐mir‐375 to miR-375

Cell & Bioscience ◽

10.1186/s13578-020-00526-9 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Haoyu Wang ◽

Jing Yuan ◽

Xiaoqian Dang ◽

Zhibin Shi ◽

Wenrui Ban ◽

...

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

Motor Function ◽

Critical Region ◽

Cell Model ◽

Spinal Cord Tissue ◽

Spinal Cord Neurons ◽

Cord Injury ◽

Neuron Apoptosis

Abstract Background Spinal cord injury (SCI) is a disabling disorder, resulting in neurological impairments. This study investigated the mechanism of methyltransferase-like 14 (Mettl14) on apoptosis of spinal cord neurons during SCI repair by mediating pri-microRNA (miR) dependent N6-methyladenosine (m6A) methylation. Methods The m6A content in total RNA and Mettl14 levels in spinal cord tissues of SCI rats were detected. Mettl14 expression was intervened in SCI rats to examine motor function, neuron apoptosis, and recovery of neurites. The cell model of SCI was established and intervened with Mettl14. miR-375, related to SCI and positively related to Mettl14, was screened out. The expression of miR-375 and pri-miR-375 after Mettl14 intervention was detected. The expression of pri-miR-375 combined with DiGeorge critical region 8 (DGCR8) and that modified by m6A was detected. Furthermore, the possible downstream gene and pathway of miR-375 were analysed. SCI cell model with Mettl14 intervention was combined with Ras-related dexamethasone-induced 1 (RASD1)/miR-375 intervention to observe the apoptosis. Results Mettl14 level and m6A content in spinal cord tissue were significantly increased. After Mettl14 knockdown, the injured motor function was restored and neuron apoptosis was reduced. In vitro, Mettl14 silencing reduced the apoptosis of SCI cells; miR-375 was reduced and pri-miR-375 was increased; miR-375 targeted RASD1. Silencing Mettl14 inactivated the mTOR pathway. The apoptosis in cells treated with silencing Mettl14 + RASD1/miR-375 was inhibited. Conclusions Mettl14-mediated m6A modification inhibited RASD1 and induced the apoptosis of spinal cord neurons in SCI by promoting the transformation of pri-miR-375 to mature miR-375.

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