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Background: To comprehensively assess the neurologic recovery potential of chondroitinase ABC (ChABC) in rats after spinal cord injury (SCI)., Methods: The PubMed, Embase, ScienceDirect, Web of Science, and China National Knowledge Infrastructure databases were searched for animal experiments that evaluated the use of ChABC in the treatment of SCI up to November 2022. Studies reporting neurological function using the Basso, Beattie, and Bresnahan (BBB) scale, as well as assessments of cavity area, lesion area, and glial fibrillary acidic protein (GFAP) levels, were included in the analysis., Results: A total of 46 studies were ultimately selected for inclusion. The results of the study showed that rats with SCI that received ChABC therapy exhibited a significant improvement in locomotor function after 7 days compared with controls (32 studies, weighted mean difference (WMD) = 0.58, [0.33, 0.83], p  < 0.00001). Furthermore, the benefits of ChABC therapy were maintained for up to 28 days according to BBB scale. The lesion area was reduced by ChABC (5 studies, WMD = -20.94, [-28.42, -13.46], p  < 0.00001). Meanwhile, GFAP levels were reduced in the ChABC treatment group (8 studies, WMD = -29.15, [-41.57, -16.72], p <  0.00001). Cavity area is not statistically significant. The subgroup analysis recommended that a single injection of 10 μL (8 studies, WMD = 2.82, [1.99, 3.65], p <  0.00001) or 20 U/mL (4 studies, WMD = 2.21, [0.73, 3.70], p =  0.003) had a better effect on improving the function. The funnel plot of the BBB scale was found to be essentially symmetrical, indicating a low risk of publication bias., Conclusions: This systematic review and meta-analysis has indicated that ChABC could improve functional recovery in rats after SCI.

Context: Spinal cord injury (SCI) is a potentially fatal neurological disease with severe complications and a high disability rate. An increasing number of animal experimental studies support the therapeutic effect of quercetin, which is a natural anti-inflammatory and antioxidant bioflavonoid., Objective: This paper reviewed the therapeutic effect of quercetin on a rat SCI model and summarized the relevant mechanistic research., Data Sources: PubMed, EMBASE, Web of Science, Science Direct, WanFang Data, SinoMed databases, the China National Knowledge Infrastructure, and the Vip Journal Integration Platform were searched from their inception to April 2023 for animal experiments applying quercetin to treat SCI., Study Selection: Based on the PICOS criteria, a total of 18 eligible studies were included, of which 14 were high quality., Results: In this study, there was a gradual increase in effect based on the Basso, Beattie, and Bresnahan (BBB) score after three days ( p  < 0.0001). Furthermore, gender differences also appeared in the efficacy of quercetin; males performed better than females ( p  = 0.008). Quercetin was also associated with improved inclined plane test score ( p  = 0.008). In terms of biochemical indicators, meta-analysis showed that MDA ( p  < 0.0001) and MPO ( p  = 0.0002) were significantly reduced after quercetin administration compared with the control group, and SOD levels were increased ( p  = 0.004). Mechanistically, quercetin facilitates the inhibition of oxidative stress, inflammation, autophagy and apoptosis that occur after SCI., Conclusions: Generally, this systematic review suggests that quercetin has a neuroprotective effect on SCI.

Ethnopharmacological Relevance: The Shenqisherong (SQSR) pill is an empirical prescription of traditional Chinese medicine (TCM), which originated from the National Chinese Medical Science Master, Shi Qi. It has been widely used in the treatment of cervical spondylotic myelopathy (CSM) and promote the recovery of spinal cord function, but underlying molecular mechanism remains unclear., Aim of the Study: The objective of this study was to confirm the neuroprotective effects of the SQSR pill., Materials and Methods: A rat model of chronic compression at double-level cervical cord was used in vivo. The protective role of SQSR pill on CSM rats was measured by Basso, Beattie, and Bresnahan (BBB) locomotor scale, inclined plane test, forelimb grip strength assessment, hindlimb pain threshold assessment, and gait analysis. The levels of reactive oxygen species (ROS) were examined by Dihydroethidium (DHE) staining and 2',7'-Dichlorofluorescein (DCF) assay, and apoptosis was detected by TdT-mediated dUTP nick-end labeling (TUNEL) assay. The expression of apoptosis proteins was evaluated by immunofluorescence staining and Western blot., Results: SQSR pill could facilitate locomotor function recovery in rats with chronic cervical cord compression, reduce local ROS in the spinal cord and downregulate the c-Jun-N-terminal kinase (JNK)/caspase-3 signaling pathway. In addition, the SQSR pill could protect primary rat cortical neurons from glutamate-treated toxicity in vitro by reducing the ROS and downregulating the phosphorylation of JNK and its downstream factors related to neuronal apoptosis meditated by the caspase cascade. Then, the neuroprotective effect was counteracted by a JNK activator., Conclusions: Together, SQSR pill could ameliorate neuronal apoptosis by restraining ROS accumulation and inhibiting the JNK/caspase-3 signaling pathway, indicating that SQSR pill could be a candidate drug for CSM., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Spinal cord injury (SCI) is one of the most disabling neurological conditions, afflicting thousands of human beings. Edaravone, a well-known reactive oxygen species scavenger, is expanding its new scope in field of SCI. The objective of this systematic review is to determine the neuroprotective effects and discuss the underlying mechanism of edaravone in management of SCI., Methods: The systematic review will include the controlled studies evaluating the neurological roles of edaravone on experiment rat models following SCI. The primary outcome will be the 21-point Basso, Beattie, and Bresnahan locomotor rating scale. The secondary outcomes will include the preservation of white matter areas and malondialdehyde levels. Two researchers will independently search PubMed, Embase, Web of Science, Scopus and Cochrane Library from their inception date. Following study selection, data extraction, and assessment of methodological quality in included studies using the SYRCLE's RoB tool, data from eligible studies will be pooled and analyzed using random-effects models with RevMan 5.3 software. In case of sufficient data, subgroup analyses with respect to species, age, gender, injury characteristics, or administration details will be carried out to explore the factors modifying efficacy of edaravone. For exploring the appropriate dose of edaravone, a network meta-analysis approach will be conducted based on the Bayesian method. Importantly, the proposed mechanisms and changes of related molecules will be also extracted from included studies for comprehensively investigating the mechanisms underlying the neuroprotective effects of edaravone., Discussion: In this study, we aim to quantitatively analyze the role of edaravone in locomotor recovery and tissue damage in SCI rat model. The efficacy of edaravone in distinct scenarios will be investigated by subgroup analyses, and we expect to predict the candidate dose that offers a superior treatment effect using network meta-analyses. Moreover, a comprehensive framework regarding the neuroprotective mechanisms behind edaravone will be constructed via a combination of systematic and traditional review. This study will bring implications for future preclinical studies and clinical applications of SCI. Nonetheless, in light of the anticipated limitations in animal experimental design and methodological quality, the results in this review should be interpreted with caution., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Cervical spondylotic myelopathy (CSM) is a severe non-traumatic spinal cord injury (SCI) wherein the spinal canal and cervical cord are compressed due to the degeneration of cervical tissues. To explore the mechanism of CSM, the ideal model of chronic cervical cord compression in rats was constructed by embedding a polyvinyl alcohol-polyacrylamide hydrogel in lamina space. Then, the RNA sequencing technology was used to screen the differentially expressed genes (DEGs) and enriched pathways among intact and compressed spinal cords. A total of 444 DEGs were filtered out based on the value of log 2 (Compression/Sham); these were associated with IL-17, PI3K-AKT, TGF-β, and Hippo signaling pathways according to the GSEA, KEGG, and GO analyses. Transmission electron microscopy indicated the changes in mitochondrial morphology. Western blot and immunofluorescence staining revealed neuronal apoptosis, astrogliosis and microglial neuroinflammation in the lesion area. Specifically, the expression of apoptotic indicators, such as Bax and cleaved caspase-3, and inflammatory cytokines, such as IL-1β, IL-6, and TNF-α, were upregulated. The activation of IL-17 signaling pathway was observed in microglia instead of neurons or astrocytes, the activation of TGF-β and inhibition of Hippo signaling pathways were detected in astrocytes instead of neurons or microglia, and the inhibition of PI3K-AKT signaling pathway was discovered in neurons rather than microglia of astrocytes in the lesion area. In conclusion, this study indicated that neuronal apoptosis was accompanied by inhibiting of the PI3K-AKT pathway. Then, the activation of microglia IL-17 pathway and NLRP3 inflammasome effectuated the neuroinflammation, and astrogliosis was ascribed to the activation of TGF-β and the inhibition of the Hippo pathway in the chronic cervical cord of compression. Therefore, therapeutic methods targeting these pathways in nerve cells could be promising CSM treatments., Competing Interests: Declaration of competing interest The author states that there is no conflict of interest., (Copyright © 2023 Longhua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine. Published by Elsevier Ltd.. All rights reserved.)

Spinal cord injury (SCI) is a serious disabling condition that leads to the loss of motor, sensory, and excretory functions, seriously affecting the quality of life of patients and imposing a heavy burden on the patient's family and society. There is currently a lack of effective treatments for SCI. However, a large number of experimental studies have shown beneficial effects of tetramethylpyrazine (TMP). We performed a meta-analysis to systematically evaluate the effects of TMP on neurological and motor function recovery in rats with acute SCI. English (PubMed, Web of Science, and EMbase) and Chinese (CNKI, Wanfang, VIP, and CBM) databases were searched for literature related to TMP treatment in rats with SCI published until October 2022. Two researchers independently read the included studies, extracted the data, and evaluated their quality. A total of 29 studies were included, and a risk of bias assessment revealed that the methodological quality of the included studies was low. The results of the meta-analysis showed that the Basso, Beattie, and Bresnahan (BBB; n = 429, pooled mean difference [MD] = 3.44, 95% confidence interval [CI] = 2.67 to 4.22, p < 0.00001) and inclined plane test (n = 133, pooled MD = 5.60, 95% CI = 3.78 to 7.41, p < 0.00001) scores of rats treated with TMP were significantly higher than those in the control group at 14 days after SCI. TMP treatment also resulted in a significant reduction in malondialdehyde (MDA; n = 128, pooled MD = -2.03, 95% CI = -3.47 to -0.58, p < 0.00001) and increased superoxide dismutase (SOD; n = 128, pooled MD = 5.02, 95% CI = 2.39 to 7.65, p < 0.00001). Subgroup analysis indicated that different doses of TMP did not improve the BBB scale and inclined plane test angles. In conclusion, this review showed that TMP can improve SCI outcomes; however, in view of the limitations of the included studies, larger and high-quality studies are required for verification., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Spinal cord injury (SCI) is a devastating condition that has few treatment options. Riluzole, a sodium channel blocker used to treat amyotrophic lateral sclerosis, has been initially trialed in human SCI. We performed a systematic review to critically assess the efficacy of riluzole in locomotor recovery and damage extension in SCI rat models, and the potential for clinical translation. PubMed, Embase, Cochrane Library, and Chinese databases were searched from their inception date to March 2018. Two reviewers independently selected animal studies that evaluated neurological recovery and lesion area following riluzole treatment in SCI rat models, extracted data and assessed methodological quality. Pairwise meta-analysis, subgroup analysis, and network meta-analysis were performed to assess the effects of riluzole on SCI. Ten eligible studies were included. Two studies had high methodological quality. Overall, the Basso, Beattie, and Bresnahan scores were increased in riluzole-treated animals versus controls, and effect sizes showed a gradual increase from the 1st (five studies, n = 104, mean difference = 1.24, 95% CI = 0.11 to 2.37, p = 0.03) to 6th week after treatment (five studies, n = 120, mean difference = 2.34, 95% CI = 1.26 to 3.42, p < 0.0001). Riluzole was associated with improved outcomes in the inclined plane test and the tissue preservation area. Subgroup analyses suggested an association of locomotor recovery with riluzole dose. Network meta-analysis showed that 5 mg/kg riluzole exhibited greater protection than 2.5 and 8 mg/kg riluzole. Collectively, this review suggests that riluzole has a protective effect on SCI, with good safety and a clear mechanism of action and may be suitable for future clinical trials or applications. However, animal results should be interpreted with caution given the known limitations in animal experimental design and methodological quality., (© 2019 International Society for Neurochemistry.)

Spinal cord injury is a serious trauma of the spinal and nervous system, local tissue destruction and microcirculation disturbance can lead to a more serious spinal cord injury and extensive necrosis of neurons. Spinal cord injury often accompany with Inflammation reaction producing a variety of cytokines and bioactive substances, result in macrophage polarization. M1 macrophages polarization are induced by IFN-γ, LPS, TNF-α and so on, it show the damage and proinflammatory effect. M2 macrophages polarization are caused by IL-4, IL-10, IL-13 and show the recovery and anti-inflammatory effect. However, clinical treatment after spinal cord injury is very limited, inhibition of proinflammatory and promotion of anti-inflammatory by regulating the M1 macrophages and M2 macrophages is a new direction for the treatment of spinal cord injury. The article will review different phenotype and function of macrophages after spinal cord injury., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© 2018 by the China Journal of Orthopaedics and Traumatology Press.)

Spinal cord injury (SCI) leads to loss of function below the lesion and affects individuals worldwide. An increasing number of experimental studies support the effectiveness of melatonin (MT) for SCI. Our objectives were to investigate neurological recovery and anti-oxidant effects of MT in animal models of SCI, and to explore the appropriate dose. Published MT studies in SCI animal models described in six databases were searched. Two practiced investigators selected the studies, extracted the data, and independently evaluated the quality of the included studies. A meta-analysis evaluated the effect of MT in SCI and a network meta-analysis was performed to explore the appropriate MT dose for SCI models. Thirteen studies were analyzed, of which three were high quality. The results of the meta-analysis manifested that the behavioral evaluation (Basso, Beattie, and Bresnahan scales, n = 90, p = 0.003; motor function scores, n = 92, p = 0.004; Tarlov's criteria, n = 150, p = 0.002; inclined plane test, n = 150, p = 0.001) and biochemical outcomes (malondialdehyde, n = 121, p = 0.0010; glutathione levels, n = 64, p < 0.0001; and myeloperoxidase activity, n = 32, p < 0.00001) were improved, compared with the control group, after MT administration. A dose of 12.5 mg/kg was most effective in SCI rat models. Studies indicated that MT administration significantly improved neurological recuperation and anti-oxidant effects in rat models of SCI. The appropriate dose of MT was 12.5 mg/kg for SCI rat models. The majority of included studies were low quality; however, optimal MT treatment in SCI still requires high quality studies.

Spinal cord injury (SCI) is a devastating condition affecting young, healthy individuals worldwide. Existing agents have inadequate therapeutic efficacy, and some are associated with side effects. Our objective is to summarize and critically assess the neurological recovery and antioxidant effects of curcumin for treatment of SCI in rat models. PubMed, Embase, and Chinese databases were searched from their inception date to February 2014. Two reviewers independently selected animal studies that evaluated neurological recovery and antioxidant effects of curcumin, compared to placebo, in rats with SCI, extracted data, and assessed the methodological quality. A pair-wise analysis and a network meta-analysis were performed. Eight studies with adequate randomization were selected and included in the systematic review. Two studies had a higher methodological quality. Overall, curcumin appears to significantly improve neurological function, as assessed using the Basso, Beattie, Bresnahan (BBB) locomotor rating scale (four studies, n=132; pooled mean difference [MD]=3.09; 95% confidence interval [CI], 3.40-4.45; p=0.04), in a random-effects model and decrease malondialdehyde (MDA) using a fixed-effects model (four studies, n=56; pooled MD=-1.00; 95% CI=-1.59 to -0.42; p=0.00008). Effect size, assessed using the BBB scale, increased gradually with increasing curcumin dosage. The difference between low- and high-dose curcumin using the BBB scale was statistically significant. Neurological recovery and antioxidant effects of curcumin were observed in rats with SCI despite poor study methodological quality.