scholarly journals The effect of lithium chloride on the motor function of spinal cord injury–controlled rat and the relevant mechanism

2019 ◽  
Vol 17 ◽  
pp. 205873921985285
Author(s):  
Gang Chen ◽  
Yimin Liang ◽  
Fanghu Chen ◽  
Haifeng Wang ◽  
Guoming Zhu
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Lithium Chloride ◽  
Sham Operation ◽  
Model Group ◽  
Nissl Staining ◽  
Sham Operation Group ◽  
Significant Difference ◽  
Cord Injury ◽  
Operation Group

The objective of this study is to discuss the effect and mechanism of lithium chloride on the rehabilitation of locomotion post spinal cord injury (SCI) by observing the effect of lithium chloride on the expression of the brain-derived neurotrophic factor (BDNF)/tropomyosin receptor kinase B (TrkB) pathway. In total, 36 Sprague-Dawley (SD) rats were randomly divided into the sham operation group (n = 12), model group (n = 12), and lithium chloride group (n = 12). The sham operation group underwent laminectomy, while for the model group and the lithium chloride group with the NYU spinal cord impactor the SCI model was established. Basso, Beattie, and Bresnahan (BBB) score was used to evaluate locomotion after administration for 1, 3, 5, and 7 days, and the tissues were gathered for Nissl staining, transmission electron microscopy, immunofluorescence, and Western blot. With a statistical difference ( P < 0.05) on the 3rd day and significant difference ( P < 0.01) on the 5th day post administration, a higher BBB score was observed in the lithium chloride group indicating that lithium chloride improved the locomotion function after SCI. A better structure and morphology of neuron were observed by Nissl staining in the lithium chloride group. Lithium chloride promoted BDNF secretion from neurons in the spinal cord anterior horn with a significant difference compared to the model group ( P < 0.01). Compared with the model group, lithium chloride significantly promoted the expression of BDNF protein and phosphorylated TrkB protein ( P < 0.05), but no difference in the expression of TrkB was detected. Lithium chloride can alleviate the locomotion function after SCI with a mechanism that it can promote BDNF secretion from neurons in the spinal cord anterior horn and phosphorylation of TrkB to upregulate the BDNF/TrkB pathway supporting survival of neurons and regeneration and remyelination of axons.

Resveratrol on the Inflammatory Environment of Rat Bone Marrow Mesenchymal Cells

2021 ◽  
Vol 11 (10) ◽  
pp. 1932-1939
Author(s):  
Shaofeng Tang ◽  
Nvzhao Yao ◽  
Dahai Qin
Keyword(s):  
Spinal Cord ◽  
Sham Group ◽  
Inflammatory Factors ◽  
Sham Operation ◽  
Spinal Cord Tissue ◽  
Sham Operation Group ◽  
Western Blot Method ◽  
Cord Injury ◽  
Operation Group ◽  
Bone Marrow Mesenchymal Cells

Our study assesses the mechanism of Sirt-1 signaling pathway and inflammation changes after spinal cord injury (SCI). SD rats were assigned into Sham group and SCI group. The Sham group only received bites off the corresponding vertebral lamina without the blow operation. The Western Blot method was used to detect Sirt-1 level, ELISA analyzed IL-1β and IL-6 level in the spinal cord tissues along with measuring Sirt-1 and TNF-α level by immunofluorescence staining. Sirt-1 changed with the time after SCI and was significantly higher than sham operation group at 1 day after injury, reaching the highest level at 3 days followed by a decrease. IL-1β and IL-6 after SCI was significantly higher than sham operation group at 1 day after injury. Immunofluorescence double staining showed that Sirt-1 and TNF-α expression in spinal cord tissue after injury were upregulated. The expression of Sirt-1 changed with time after SCI, and was consistent with the trend of changes in inflammatory factors. In conclusion, Sirt-1 is related to the changes of inflammatory factors after SCI, indicating that Sirt-1 may be involved in inflammation after SCI.

scholarly journals Transcriptomic analysis of α-synuclein knockdown after T3 spinal cord injury in rats

2019 ◽  
Author(s):  
Hong Zeng ◽  
Bao-fu Yu ◽  
Nan Liu ◽  
Yan-yan Yang ◽  
Hua-yi Xing ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Lentiviral Vector ◽  
Cell Junction ◽  
Receptor Interaction ◽  
Sham Operation ◽  
Rna Seq ◽  
Sprague Dawley ◽  
Sham Operation Group ◽  
Cord Injury

Abstract Abstract Background Endogenous α-synuclein (α-Syn) is involved in many pathophysiological processes in the secondary injury stage after acute spinal cord injury (SCI), and the mechanism governing these functions has not been thoroughly elucidated to date. This research aims to characterize the effect of α-Syn knockdown on transcriptional levels after SCI and to determine the mechanisms underlying α-Syn activity based on RNA-seq. Result The establishment of a rat model of lentiviral vector-mediated knockdown of α-Syn in Sprague-Dawley rats with T3 spinal cord contusion. The results of the RNA-SEQ analysis showed that there were 191 differentially expressed genes (DEGs) between the SCI group and the LV_SCI group, and 96 DEGs in the LV_SCI group compared with the sham operation group (CON group). The top 20 biological transition terms were identified by Gene ontology (GO) analysis. The Kyoto Gene and Genomic Encyclopedia (KEGG) analysis showed that the LV_SCI group significantly up-regulated the cholinergic synaptic pathway and the neuroactive ligand receptor interaction signaling pathway. Enriched chord analysis analyzes key genes. Further cluster analysis, gene and protein interaction network analysis showed that Chrm2 and Chrnb2 together observed the LV_SCI group to promote the proliferation of Chrm2 and Chrnb2 and the neurogenesis of the injury site by immunofluorescence. Further by subcellular localization, the LV_SCI group enhanced the expression of Chrnb2 at the cell membrane and cell junction. Conclusion Knockdown of α-synuclein after spinal cord injury enhance motor function and promote neurogenesis probably through enhancing cholinergic signaling pathways and neuroreceptor interactions. This study not only further clarifies the understanding of the mechanism of knockdown of α-synuclein on SCI but also helps to guide the treatment strategy for SCI.

scholarly journals MiR-139-5p alleviates neural cell apoptosis induced by spinal cord injury through targeting TRAF3

2020 ◽  
Author(s):  
Ziying Zhang ◽  
Lifang Shen ◽  
Yingying Yan
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Functional Recovery ◽  
Cell Apoptosis ◽  
Target Genes ◽  
Neural Cell ◽  
Sham Operation ◽  
Sham Operation Group ◽  
Cord Injury

Spinal cord injury (SCI) is a neurological trauma that causes loss of locomotor function and sensory deficit. Previous studies showed that miRNAs play a crucial role in SCI. This study further evaluated the potential role of miR-139-5p in the neural cell apoptosis after SCI in rats. A rat SCI model was successfully established and miR-139-5p expression level in SCI rats was down-regulated compared to the sham group (sham operation group) determined by qRT-PCR. MiR-139-5p overexpression via administration with miR-139-5p agomir improved locomotor functional recovery, attenuated allodynia and hyperalgesia and alleviated neural cell apoptosis in SCI rats. In addition, TRAF3 (TNF receptor-associated factor 3 ) was identified to be a target of miR-139-5p by searching the proposed target genes in TargetScan 7.1 database. Co-transfection of miR-139-5p agomir and adenovirus of TRAF3 plasmids significantly improved functional recovery and alleviated neural cell apoptosis. Therefore, TRAF3 mediated the anti-apoptosis effect of miR-139-5p in SCI rats and miR-139-5p could be a promising candidate for SCI therapy by alleviating neural cell apoptosis through targeting TRAF3.

scholarly journals Expression of Slit and Robo During Remodeling of Corticospinal Tract in Cervical Spinal Cord in Middle Cerebral Artery Occlusion Rats

2021 ◽  
Author(s):  
Zhenhao Ying ◽  
Junxuan Wu ◽  
Wenjun Jiang ◽  
Guoli Zhang ◽  
Weiming Zhu ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Motor Function ◽  
Corticospinal Tract ◽  
Cervical Spinal Cord ◽  
Artery Occlusion ◽  
Sham Operation ◽  
Model Group ◽  
Sham Operation Group ◽  
Operation Group ◽  
Cerebral Artery Occlusion

Abstract Background: Slits and Robos were associated with the generation of axons of corticospinal tract during the corticospinal tract (CST) remodeling after the cerebral ischemic stroke (CIS). However, little is known about the mechanism of CST remodeling. In this study, we detected the expression of Slits and Robos in middle cerebral artery occlusion (MCAO) rats to investigate the roles of Slits and Robos in the CIS. Methods: MCAO model was established using modified Zea Longa method. Beam walking test (BWT) was conducted to evaluate the motor function. The images of the track of cortical spinal cord beam on day 7, 14 and 21 were observed by anterograde CST tracing. Biopinylated dextan amine (BDA) was used to mark CST anterogradely. Expression of GAP-43 mRNA and GAP-43 protein in cervical spinal cord was detected by Real-Time PCR and Western blot analysis, respectively. The expression of Slit1, Slit2 and Robo1 in cervical spinal cord was detected by immunofluorescence staining.Results: The scores in the model group were significantly reduced compared to sham-operation group on day 7 (P<0.001), 14 (P<0.001) and 21 (P<0.001), respectively. There was no significant difference in the score on day 7, 14 and 21 of the sham-operation groups (P>0.05). In contrast, significant increase was noticed in the scores in model group, presenting a time-dependent manner. More CST staining fibers could be observed at the degenerative side in the model group compared with that of the sham-operation group on day 21. GAP-43 mRNA expression in the model group showed significant increase compared to that of sham-operation group on day 14 (P=0.015) and 21 days (P=0.002). The expression of GAP-43 protein in model group showed significant increase compared to that of sham-operation group on day 14 (P=0.022) and day 21 (P=0.008), respectively. The expression of Slit1 and Slit2 showed increase on day 14 and day 21, while the expression of Robo1 showed significant decrease in MCAO rats.Conclusion: Up-regulation of Slit1 and Slit2 and the downregulation of Robo1 may be related to the axons of CST midline crossing in spinal cord of MCAO rat during the spontaneous recovery of impaired motor function.

Lithium Chloride Facilitates Autophagy Following Spinal Cord Injury via ERK-dependent Pathway

2017 ◽  
Vol 32 (4) ◽  
pp. 535-543 ◽  
Author(s):  
Peilin Liu ◽  
Zijuan Zhang ◽  
Qingde Wang ◽  
Rundong Guo ◽  
Wei Mei
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Lithium Chloride ◽  
Cord Injury ◽  
Dependent Pathway

scholarly journals The effectiveness and safety of LMWH for preventing thrombosis in patients with spinal cord injury: a meta-analysis

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Ze Lin ◽  
Yun Sun ◽  
Hang Xue ◽  
Lang Chen ◽  
Chenchen Yan ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Venous Thrombosis ◽  
Meta Analysis ◽  
Therapeutic Effects ◽  
Significant Difference ◽  
Cord Injury ◽  
Review Manager ◽  
Evident Difference

Abstract Background Unfractionated heparin (UFH) and low molecular weight heparin (LMWH) are commonly used for preventing venous thrombosis of the lower extremity in patients with traumatic spinal cord injury. Although, LMWH is the most commonly used drug, it has yet to be established whether it is more effective and safer than UFH. Further, a comparison of the effectiveness of LMWH in preventing thrombosis at different locations and different degrees of spinal cord injury has also not been clearly defined. Materials and methods Cohort studies comparing the use of LMWH and UFH in the prevention of lower limb venous thrombosis in patients with spinal cord injury were identified using PubMed. The risk of bias and clinical relevance of the included studies were assessed using forest plots. The Newcastle-Ottawa quality assessment scale was used to evaluate the quality of the included studies. The main results of the study were analyzed using Review Manager 5.3. Results A total of five studies were included in this meta-analysis. Four studies compared the effectiveness and safety of LMWH and UFH in preventing thrombosis in patients with spinal cord injury. No significant differences were found between the therapeutic effects of the two drugs, and the summary RR was 1.33 (95% CI 0.42–4.16; P = 0.63). There was also no significant difference in the risk of bleeding between the two medications, and the aggregate RR was 0.78 (95% CI 0.55–1.12; P = 0.18). When comparing the efficacy of LMWH in preventing thrombosis in different segments and different degrees of spinal cord injury, no significant differences were found. Conclusions The results of this analysis show that compared with UFH, LMWH has no obvious advantages in efficacy nor risk prevention, and there is no evident difference in the prevention of thrombosis for patients with injuries at different spinal cord segments.

scholarly journals Exendin-4 improves neuron protection and functional recovery in experimental spinal cord injury in rats through regulating PCBP2 expression

2020 ◽  
Author(s):  
Huaichao Luo ◽  
Qingwei Wang ◽  
Lei Wang
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Cell Apoptosis ◽  
Sham Group ◽  
Sham Operation ◽  
Therapeutic Effects ◽  
Rat Models ◽  
Apoptosis Rate ◽  
Cord Injury ◽  
Group A

AbstractAimsIn the present research, we assessed the therapeutic effects of Exendin-4 (Ex-4) on rat models with spinal cord injury (SCI).Materials and methods36 male Sprague–Dawley rats were randomly allocated into three groups, including sham operation group, SCI group and SCI+Ex-4 group (Ex-4 treatment (10 µg/rat) after SCI, i.p.). In the SCI group, a laminectomy was performed at the T10 vertebrae, followed by weight-drop contusion of the spinal cord. In the sham group, a laminectomy was carried out without SCI contusion.Key findingsOur results showed that Basso-Beattie-Bresnahan scale scores were significantly decreased after SCI, and were obviously improved in SCI rats with Ex-4 administration. Additionally, the water content of spinal cord in SCI group was dramatically increased than that in sham group, and after Ex-4 treatment, degree of edema of spinal cord was remarkably reduced. And also, concentration levels of inflammatory cytokines (IL-1α, IL-1β, IL-6 and TNF-α) in the spinal cord were significantly elevated after SCI, and were remarkably reduced in SCI rats with Ex-4 administration. Subsequently, cell apoptosis rate in the injured spinal cord was significantly increased, and after Ex-4 treatment, cell apoptosis rate was remarkably decreased. We also revealed that levels of PCBP2 mRNA and protein were significantly up-regulated after SCI, and were dramatically dropped in SCI rats with Ex-4 administration.SignificanceTake altogether, our findings disclosed that Ex-4 plays a role in promoting neurological function recovery and inhibiting neuronal apoptosis through effecting PCBP2 expression in SCI rat models.

The therapeutic window for spinal cord decompression in a rat spinal cord injury model

2005 ◽  
Vol 3 (4) ◽  
pp. 302-307 ◽  
Author(s):  
Christopher B. Shields ◽  
Y. Ping Zhang ◽  
Lisa B. E. Shields ◽  
Yingchun Han ◽  
Darlene A. Burke ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Spinal Stenosis ◽  
Spinal Cord Compression ◽  
Cord Compression ◽  
Therapeutic Window ◽  
Content Type ◽  
Significant Difference ◽  
Cord Injury ◽  
Fine Print

Object. There are no clinically based guidelines to direct the spine surgeon as to the proper timing to undertake decompression after spinal cord injury (SCI) in patients with concomitant stenosis-induced cord compression. The following three factors affect the prognosis: 1) severity of SCI; 2) degree of extrinsic spinal cord compression; and 3) duration of spinal cord compression. Methods. To elucidate further the relationship between varying degrees of spinal stenosis and a mild contusion-induced SCI (6.25 g-cm), a rat SCI/stenosis model was developed in which 1.13- and 1.24-mm-thick spacers were placed at T-10 to create 38 and 43% spinal stenosis, respectively. Spinal cord damage was observed after the stenosis—SCI that was directly proportional to the duration of spinal cord compression. The therapeutic window prior to decompression was 6 and 12 hours in the 43 and 38% stenosis—SCI lesions, respectively, to maintain locomotor activity. A significant difference in total lesion volume was observed between the 2-hour and the delayed time(s) to decompression (38% stenosis—SCI, 12 and 24 hours, p < 0.05; 43% stenosis—SCI, 24 hours, p < 0.05) indicating a more favorable neurological outcome when earlier decompression is undertaken. This finding was further supported by the animal's ability to support weight when decompression was performed by 6 or 12 hours compared with 24 hours after SCI. Conclusions. Analysis of the findings in this study suggests that early decompression in the rat improves locomotor function. Prolongation of the time to decompression may result in irreversible damage that prevents locomotor recovery.

Cervical Spinal Cord Injury Shows Markedly Lower than Predicted Mortality (>72 Hours After Multiple Trauma) From Sepsis and Multiple Organ Failure

2018 ◽  
Vol 35 (4) ◽  
pp. 378-382
Author(s):  
Oliver Kamp ◽  
Oliver Jansen ◽  
Rolf Lefering ◽  
Renate Meindl ◽  
Christian Waydhas ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Multiple Organ Failure ◽  
Organ Failure ◽  
Multiple Trauma ◽  
Injury Severity ◽  
Multiple Organ ◽  
Injury Pattern ◽  
Significant Difference ◽  
Cord Injury

Background: Sepsis and multiple organ failure (MOF) remain one of the main causes of death after multiple trauma. Trauma- and infection-associated immune reactions play an important role in the pathomechanism of MOF, but the exact pathways remain unknown. Spinal cord injury (SCI) may lead to an altered immune response, and some studies suggest a prognostic advantage for such patients having sepsis or multiple trauma. Yet these findings need to be evaluated in larger cohorts of trauma patients. Methods: Retrospective, multicenter study, using the data of the TraumaRegister DGU. Patients with and without SCI surviving the initial first 72 hours after trauma were matched according to injury pattern and age. Comparative analysis considered morbidity (sepsis, MOF) and hospital mortality. Results: The study population included 800 matched pairs. As intended by the matching process, patients with cervical SCI had an otherwise comparable injury pattern but a higher severity of trauma (mean Injury Severity Score: 36 vs 29, mean number of diagnosis: 5.6 vs 4.4). They had a higher rate of sepsis (15.9% vs 10.9%, P = .005) and MOF (35.9% vs 24.1%, P < .001) while mortality revealed no significant difference (9.5% vs 9.9%, P = .866). Conclusions: Cervical SCI leads to an increased rate of sepsis and MOF but appears to be favorable with respect to outcome of sepsis and MOF following multiple trauma. Further research should focus on the pathomechanisms and the possible arising therapeutic options.

scholarly journals Fire Needle Acupuncture Regulates Wnt/ERK Multiple Pathways to Promote Neural Stem Cells to Differentiate into Neurons in Rats with Spinal Cord Injury

2019 ◽  
Vol 18 (3) ◽  
pp. 245-255 ◽  
Author(s):  
Jiachun Xu ◽  
Suli Cheng ◽  
Zhaohua Jiao ◽  
Zhiheng Zhao ◽  
Zhimin Cai ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Motor Ability ◽  
Model Group ◽  
Locomotor Function ◽  
Gene And Protein Expression ◽  
Cord Injury ◽  
Fire Needle ◽  
Potential Methods ◽  
Needle Acupuncture

Background & Objective: NSCs therapy is considered one of the most potential methods for spinal cord injury (SCI). Methods: We build the SCI model rats to investigate the therapeutic effect of fire needle acupuncture in improving the locomotor function of SCI rats and its possible mechanism. BBB scale was used for the motor ability of rats. The expression of Nestin, NSE, Gal-C, and GFAP was detected by immunohistochemistry. Wnt, GSK3β, β-catenin, ERK1/2, CyclinD1, and ngn1 were detected by western blot and PCR. The BBB score of both model group (1.20±0.94, 3.12±0.67, 5.34±1.57, 7.12±1.49) and fire needle group (1.70±0.58, 4.50±1.63, 7.53±2.41, 9.24±0.63) gradually increased after SCI. Furthermore, at d10 and d14, the fire needle group showed a significantly high score compared with that in model group at the same time (P<0.05). Fire needle increased Nestin, NSE, and Gal-C expression inhibited GFAP expression after SCI. Also, fire needle could up-regulate Wnt3a, GSK3β, β-catenin, and ngn1, and down-regulate ERK1/2, cyclinD1 gene and protein expression. Conclusion: In conclusion, fire needle could improve lower limb locomotor function of SCI rats. Also, fire needles could promote endogenous NSCs proliferation differentiating into neurons, and the mechanism might be mediated by promoting the activation of Wnt/β-catenin and inhibiting the overexpression of ERK.

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