Clomethiazole (ZENDRA, CMZ) improves hind limb motor function and reduces neuronal damage after severe spinal cord injury in rat

1999 ◽  
Vol 98 (1) ◽  
pp. 22-30 ◽  
Author(s):  
M. Farooque ◽  
J. Isaksson ◽  
D. M. Jackson ◽  
Y. Olsson
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Motor Function ◽  
Hind Limb ◽  
Neuronal Damage ◽  
Cord Injury

scholarly journals Zhenbao pill protects against acute spinal cord injury via miR-146a-5p regulating the expression of GPR17

2018 ◽  
Vol 38 (1) ◽  
Author(s):  
Yongxiong He ◽  
Bokang Lv ◽  
Yanqiang Huan ◽  
Bin Liu ◽  
Yutang Li ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Motor Function ◽  
Hind Limb ◽  
Neuronal Apoptosis ◽  
Acute Spinal Cord Injury ◽  
Luciferase Reporter Assay ◽  
Luciferase Reporter ◽  
Reporter Assay ◽  
Cord Injury

The aim of the present study was to observe the effect of zhenbao pill on the motor function of acute spinal cord injury (ASCI) rats and the molecular mechanisms involving miR-146a-5p and G-protein-coupled receptor 17 (GPR17). ASCI rat model was established by modified Allen method, and then the rats were divided into three groups. SH-SY5Y cells were cultured overnight in hypoxia condition and transfected with miR-146a-5p mimic or miR-146a-5p inhibitor. The hind limb motor function of the rats was evaluated by Basso, Beattie, Bresnahan (BBB) scoring system. Quantitative real-time PCR (qRT-PCR) and Western blot were used to detect the expression of miR-146a-5p, GPR17, inducible nitric oxide synthase (iNOS), interleukin 1β (IL-1β), and tumor necrosis factor α (TNF-α). Neuronal apoptosis was measured using flow cytometry assay. Luciferase reporter assay was performed to determine the regulation of miR-146a-5p on GPR17. Zhenbao pill could enhance hind limb motor function and attenuate the inflammatory response caused by ASCI. Moreover, zhenbao pill increased the level of miR-146a-5p and decreased GPR17 expression in vivo and in vitro. Bioinformatics software predicted that GPR17 3′-UTR had a binding site with miR-146a-5p. Luciferase reporter assay showed that miR-146a-5p had a negative regulatory effect on GPR17 expression. Knockdown of miR-146a-5p could reverse the effect of zhenbao pill on the up-regulation of GPR17 induced by hypoxia, reversed the inhibitory effect of zhenbao pill on the cell apoptosis induced by hypoxia and the recovery of zhenbao pill on hind limb motor function in ASCI rats. Zhenbao pill could inhibit neuronal apoptosis by regulating miR-146a-5p/GPR17 expression, and then promoting the recovery of spinal cord function.

scholarly journals Entinostat Improves Motor Function and Neuronal Damage Via Downregulating NLRP3 Inflammasome Activation After Spinal Cord Injury

2021 ◽  
Vol 12 ◽  
Author(s):  
Chen Dai ◽  
Bin Liu ◽  
Bibo Peng ◽  
Bo Qu ◽  
Jiezhi Lin ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Inflammatory Response ◽  
Motor Function ◽  
Nlrp3 Inflammasome ◽  
Neuronal Damage ◽  
Inflammasome Activation ◽  
Nlrp3 Inflammasome Activation ◽  
Cord Injury

Background: Spinal cord injury (SCI), a major public health problem, has no effective treatment. A large number of studies have confirmed that histone deacetylases (HDACs) are involved in the physiologic processes that occur following SCI. We tried to uncover the potential neuroprotective role of entinostat (a class I HDAC inhibitor) in SCI.Methods: We conducted a study on a preclinical mouse model of SCI and OGD-induced neuronal damage to present the role of entinostat by the analysis of motor function, histopathologic damage, local NLRP3 inflammasome activation, and neuronal damage.Results: The results showed that entinostat suppressed HDAC activation (including HDAC1 and HDAC3 expression), improved the grip strength and BMS score, spinal edema, cell death, and local NLRP3 inflammasome activation in the spinal cord following SCI. Furthermore, entinostat significantly increased OGD-inhibited neuronal activity and decreased PI-positive cells, HDAC activation, caspase-1 activation, IL-1β and IL-18 levels, and NLRP3 expression.Conclusion: In summary, we first documented that entinostat improved the motor function, histopathologic damage, and local inflammatory response and NLRP3 inflammasome activation in the spinal cord following SCI and also presented the neuroprotective role of OGD-induced neuronal damage via the NLRP3 inflammasome. Thus, our study has the potential to reveal the interaction between the HDAC and NLRP3 inflammasome in the pathologic process as well as SCI and further promote the clinical indications of HDACi entinostat and clinical treatment for the inflammatory response after SCI.

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

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.

scholarly journals Neuroprotective Effects of Human Umbilical Cord-Derived Mesenchymal Stem Cells From Different Donors on Spinal Cord Injury in Mice

2022 ◽  
Vol 15 ◽  
Author(s):  
Xu Zhu ◽  
Zhen Wang ◽  
Yi Eve Sun ◽  
Yuchen Liu ◽  
Zhourui Wu ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Cell Proliferation ◽  
Inflammatory Response ◽  
Nerve Injury ◽  
Motor Function ◽  
Hind Limb ◽  
Human Umbilical Cord ◽  
Qrt Pcr ◽  
Cord Injury

Spinal cord injury (SCI) is caused by an external force, leading to severe dysfunction of the limbs below the injured segment. The inflammatory response plays a vital role in the prognosis of SCI. Human umbilical cord mesenchymal stem cell (hUCMSC) transplantation can promote repair of SCI by reducing the inflammatory response. We previously showed that hUCMSCs from 32 donors had different inhibitory abilities on BV2 cell proliferation. In this study, three experimental groups were established, and the mice were injected with different lines of hUCMSCs. Hind limb motor function, hematoxylin-eosin (H&E) staining, immunohistochemistry, Western blot (WB), qualitative real-time polymerase chain reaction (qRT-PCR), and RNA sequencing and correlation analysis were used to investigate the effects of hUCMSC transplantation on SCI mice and the underlying mechanisms. The results showed that the therapeutic effects of the three hUCMSC lines were positively correlated with their inhibitory abilities of BV2 cell proliferation rates in vitro. The MSC_A line had a better therapeutic effect on improving the hind limb motor function and greater effect on reducing the expression of glial fibrillary acidic protein (Gfap) and ionized calcium binding adaptor molecule 1 (Iba1) and increasing the expression of neuronal nuclei (NeuN). Differentially expressed genes including Zbtb16, Per3, and Hif3a were probably the key genes involved in the protective mechanism by MSC_A after nerve injury. qRT-PCR results further verified that Zbtb16, Per3, and Hif3a expressions reduced by SCI could be reversed by MSC_A application. These results suggest that the effect of hUCMSCs transplantation on acute SCI depends on their inhibitory abilities to inflammation reaction after nerve injury, which may help to shape future use of hUCMSCs combined with improving the effectiveness of clinical transformation.

scholarly journals Pannexin-1 Characterization after Spinal Cord Injury in Rats

2020 ◽  
Author(s):  
Yu Huang ◽  
Jin Lin ◽  
Xuanwei Chen ◽  
Jianhua Lin
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Western Blot ◽  
Real Time ◽  
Motor Function ◽  
Real Time Pcr ◽  
Hind Limb ◽  
Pannexin 1 ◽  
Cord Injury

Abstract Background Pannexin-1 (Panx-1) is a homomeric membrane semi-channel mostly expressed in the central nervous system of mammals, including neurons and glial cells. Panx-1 channels are highly permeable to calcium and Adenosine Triphosphatase (ATP), it plays an important role in Hypoxic injury of cerebral ischemia through a variety of signal pathways, nerve cell apoptosis and inflammatory response. However, its specific role in spinal cord injury (SCI) is not clear. In the current study, we aimed to investigate the characterization of Panx-1 after SCI in rats, and further analysis were made on its effect and possible mechanism in SCI in order to provide the experimental evidence for potential interfering target spot on SCI therapy. Methods A rat SCI model (Allen’s model) was established by NYU Impactor-III and the hind limb motor function of rats was observed by BBB score. The expression of Panx-1 was detected by Real-time PCR and Western Blot. The correlation between Panx-1 expression and the BBB score in rats after SCI was analyzed to reveal the role of Panx-1 in SCI. Results We found that the BBB score gradually recovered after SCI, but declined significantly at day 2 after SCI. Real-time PCR and Western Blot detection showed that compared with the normal control group and the sham operation group, the expression of Panx-1 increased significantly with time after SCI, and reached a peak at day 2 after SCI. Moreover, there was a significant negative correlation between the expression of Panx-1 protein and the BBB score of rat hind limb motor function at day 1, day 2, day 3 and day 5 after SCI. Conclusions The characterization of of Panx-1 expression after SCI in rats suggests that Panx-1 had a significant effect on the motor function recovery after SCI, and it was one of the important mechanisms that aggravate the secondary injury after SCI in rats. This provided experimental basis for further exploring the potential intervention target of SCI.

Bone marrow mesenchymal stem cells-derived exosomes reduce apoptosis and inflammatory response during spinal cord injury by inhibiting the TLR4/MyD88/NF-κB signaling pathway

2021 ◽  
pp. 096032712110033
Author(s):  
Liying Fan ◽  
Jun Dong ◽  
Xijing He ◽  
Chun Zhang ◽  
Ting Zhang
Keyword(s):  
Spinal Cord ◽  
Stem Cells ◽  
Bone Marrow ◽  
Spinal Cord Injury ◽  
Mesenchymal Stem Cells ◽  
Motor Function ◽  
Inflammatory Factors ◽  
Cord Injury ◽  
Marrow Mesenchymal Stem Cells ◽  
Apoptosis And Inflammation

Spinal cord injury (SCI) is one of the most common destructive injuries, which may lead to permanent neurological dysfunction. Currently, transplantation of bone marrow mesenchymal stem cells (BMSCs) in experimental models of SCI shows promise as effective therapies. BMSCs secrete various factors that can regulate the microenvironment, which is called paracrine effect. Among these paracrine substances, exosomes are considered to be the most valuable therapeutic factors. Our study found that BMSCs-derived exosomes therapy attenuated cell apoptosis and inflammation response in the injured spinal cord tissues. In in vitro studies, BMSCs-derived exosomes significantly inhibited lipopolysaccharide (LPS)-induced PC12 cell apoptosis, reduced the secretion of pro-inflammatory factors including tumor necrosis factor (TNF)-α and IL (interleukin)-1β and promoted the secretion of anti-inflammatory factors including IL-10 and IL-4. Moreover, we found that LPS-induced protein expression of toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88) and nuclear transcription factor-κB (NF-κB) was significantly downregulated after treatment with BMSCs-derived exosomes. In in vivo studies, we found that hindlimb motor function was significantly improved in SCI rats with systemic administration of BMSCs-derived exosomes. We also observed that the expression of pro-apoptotic proteins and pro-inflammatory factors was significantly decreased, while the expression of anti-apoptotic proteins and anti-inflammatory factors were upregulated in SCI rats after exosome treatment. In conclusion, BMSCs-derived exosomes can inhibit apoptosis and inflammation response induced by injury and promote motor function recovery by inhibiting the TLR4/MyD88/NF-κB signaling pathway, which suggests that BMSCs-derived exosomes are expected to become a new therapeutic strategy for SCI.

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