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 ◽  
...  

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.

1992 ◽  
Vol 76 (1) ◽  
pp. 23-31 ◽  
Author(s):  
Michael B. Bracken ◽  
Mary Jo Shepard ◽  
William F. Collins ◽  
Theodore R. Holford ◽  
David S. Baskin ◽  
...  

✓ The 1-year follow-up data of a multicenter randomized controlled trial of methylprednisolone (30 mg/kg bolus and 5.4 mg/kg/hr for 23 hours) or naloxone (5.4 mg/kg bolus and 4.0 mg/kg/hr for 23 hours) treatment for acute spinal cord injury are reported and compared with placebo results. In patients treated with methylprednisolone within 8 hours of injury, increased recovery of neurological function was seen at 6 weeks and at 6 months and continued to be observed 1 year after injury. For motor function, this difference was statistically significant (p = 0.030), and was found in patients with total sensory and motor loss in the emergency room (p = 0.019) and in those with some preservation of motor and sensory function (p = 0.024). Naloxone-treated patients did not show significantly greater recovery. Patients treated after 8 hours of injury recovered less motor function if receiving methylprednisolone (p = 0.08) or naloxone (p = 0.10) as compared with those given placebo. Complication and mortality rates were similar in either group of treated patients as compared with the placebo group. The authors conclude that treatment with the study dose of methylprednisolone is indicated for acute spinal cord trauma, but only if it can be started within 8 hours of injury.


2011 ◽  
Vol 70 (5) ◽  
pp. 1198-1202 ◽  
Author(s):  
Abdieel Esquivel-Aguilar ◽  
Gilberto Castañeda-Hernández ◽  
Angelina Martínez-Cruz ◽  
Rebecca E. Franco-Bourland ◽  
Ignacio Madrazo ◽  
...  

Cell Cycle ◽  
2018 ◽  
Vol 17 (16) ◽  
pp. 1992-2000 ◽  
Author(s):  
Huafeng Zhang ◽  
Wengang Wang ◽  
Ning Li ◽  
Peng Li ◽  
Ming Liu ◽  
...  

2021 ◽  
Vol 2021 ◽  
pp. 1-14
Author(s):  
Shuangfei Ni ◽  
Bo Yang ◽  
Lei Xia ◽  
Huafeng Zhang

Acute spinal cord injury (ASCI) is a severe traumatic disease of the central nervous system, the underlying mechanism of which is unclear. This study was intended to study the role of EZH2 and miR-146a-5p/HIF-1α in inflammation and glycolysis after ASCI, providing reference and basis for the clinical treatment and prognosis of ASCI injury. We used lipopolysaccharide (LPS) to induce inflammation of microglia, and we constructed the ASCI animal model. qRT-PCR detected the relative expression levels of EZH2, HIF-1α, miR-146a-5p, IL-6, TNF-α, IL-17, PKM2, GLUT1, and HK2 in cells and tissues. Western blot was performed to detect the expression levels of EZH2, HIF-1α, H3K27me3, IL-6, TNF-α, IL-17, PKM2, GLUT1, and HK2. ChIP verified the enrichment of H3K27me3 in the miR-146a-5p promoter region. Bioinformatics predicted the binding sites of HIF-1α and miR-146a-5p, and dual-luciferase reporter assay verified the binding of HIF-1α and miR-146a-5p. ELISA detects the levels of inflammatory factors IL-6, TNF-α, and IL-17 in the cerebrospinal fluid of rats. The GC-TOFMS was used to detect the changes of glycolytic metabolites in the cerebrospinal fluid of rats. EZH2 could mediate inflammation and glycolysis of microglia. EZH2 regulates inflammation and glycolysis through HIF-1α. EZH2 indirectly regulated the HIF-1α expression by mediating miR-146a-5p. EZH2 mediates miR-146a-5p/HIF-1α to alleviate inflammation and glycolysis in ASCI rats. In the present study, our results demonstrated that EZH2 could mediate miR-146a-5p/HIF-1α to alleviate the inflammation and glycolysis after ASCI. Therefore, EZH2/miR-146a-5p/HIF-1α might be a novel potential target for treating ASCI.


2016 ◽  
Vol 4 (2) ◽  
pp. 175-180
Author(s):  
V. Medvediev ◽  
Yu. Senchyk ◽  
N. Draguntsova ◽  
S. Dychko ◽  
V. Tsymbaliuk

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.


2018 ◽  
Vol 13 (3) ◽  
pp. 656
Author(s):  
SeyedAhmad Naseri Alavi ◽  
Ali Meshkini ◽  
Firooz Salehpour ◽  
Javad Aghazadeh ◽  
Farhad Mirzaei

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