scholarly journals Implication of cholinergic transmission in rat model of spinal cord injury: A potential therapeutic target

2021 ◽  
Vol 18 (4) ◽  
pp. 741-745
Author(s):  
Hongzhe Liu ◽  
Lei Chang ◽  
Shuai Peng ◽  
Bin Liu ◽  
Mingyan Zhang ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Rat Model ◽  
Quantitative Polymerase Chain Reaction ◽  
Motor Deficits ◽  
Cholinergic Transmission ◽  
Binding Studies ◽  
Adult Rats ◽  
Male Adult ◽  
Cord Injury

Purpose: To assess the involvement of cholinergic transmission in the etiology of spinal cord injury (SCI) in a rat model. Methods: Male adult rats (Wistar) with body weight ranging from 200 to 250 g were equally allocated into 2 groups: test (SCI) and control (non-SCI). Clipping method was used to induce SCI. Thereafter, motor function was measured using rotarod. Each rat was sacrificed by decapitation, and the cortex was excised for use in the study of the involvement of cholinergic transmission in SCI using real time quantitative polymerase chain reaction (RT-PCR) and western blot analysis (WBA). Results: Significant upregulation in acetylcholine esterase (AChE) was observed in the cortex of SCI rats, relative to non-SCI rats (p < 0.005). Results from cholinergic receptor binding studies revealed significantly decreased maximum binding (Bmax) and dissociation constant (kd) values for muscarinic receptors in SCI rats, when compared to non-SCI rats. Moreover, the reduction in intensity of cholinergic receptors was significantly greater in the cerebral cortex of SCI group compared to non-SCI group. Conclusion: The results of this study suggested that the reduction in cortical cholinergic transmission impairs motor functions in SCI, and plays a major role in motor deficits in SCI.

scholarly journals Bethanechol versus selegiline in amelioration of spinal cord injury in a rat model: A potential therapeutic option in spinal cord injury treatment

2020 ◽  
Vol 19 (1) ◽  
pp. 83-87
Author(s):  
Guangliang Fan ◽  
Jinli Luan ◽  
Xiankuo Tang ◽  
Qimin Song
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Motor Function ◽  
Therapeutic Option ◽  
Quantitative Polymerase Chain Reaction ◽  
Binding Studies ◽  
Male Adult ◽  
Acetyl Choline ◽  
Cord Injury ◽  
And Control

Purpose: To compare the effect of bethanechol versus selegiline in ameliorating spinal cord injury (SCI) in a rat model.Methods: Male adult Wistar rats (200 – 250 g) were equally divided into 3 groups: test (SCI rats treated with bethanechol), and control reference (SCI rats treated with selegiline) and control (SCI rats treated with vehicle). SCI was induced in the rats using the clipping method. Thereafter, motor function was assessed in the rats using a rotarod. Each rat was sacrificed by decapitation, and the cortex was excised for use in the study of the involvement of cholinergic and monoaminergic transmission in SCI rats using real-time quantitative polymerase chain reaction and western blot analysis.Results: Retention time was numerically greater in rats treated with acetyl choline agonist at all rotations (10, 15 and 25 rpm) when compared to MAO A inhibitor group, but the difference was not statistically significant (p > 0.05). Both bethanechol and selegiline improved motor function by increasing cholinergic and monoaminergic transmission. Both drugs (bethanechol and selegiline) were effective in ameliorating the motor function deficit caused by spinal cord injury. A significant upregulation in acetylcholine esterase (AChE) was observed in the cortex of the SCI rats, relative to non-SCI rats (p < 0.005). Results from cholinergic receptor binding studies revealed significantly decreased Bmax and kd values for muscarinic receptors in SCI rats, when compared to non-SCI rats. Moreover, the reduction in the intensity of cholinergic receptors was significantly higher in the cerebral cortex of SCI rats than in non-SCI rats.Conclusion: Bethanechol and selegiline are effective in ameliorating motor function deficit caused by spinal cord injury in rats. Both drugs also improve motor function in SCI rats. Therefore, the drugs have potentials for use in the therapeutical management of spinal cord injury. Keywords: Spinal cord injury, Bethanechol, Selegiline, Motor functions, Monoaminergic transmission, Cholinergic transmission

scholarly journals Up-regulation of MicroRNAs-21 and -223 in a Sprague-Dawley Rat Model of Traumatic Spinal Cord Injury

2020 ◽  
Vol 10 (3) ◽  
pp. 141
Author(s):  
Hyo-Jin Chung ◽  
Wook-Hun Chung ◽  
Sun-Hee Do ◽  
Jae-Hoon Lee ◽  
Hwi-yool Kim
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Rat Model ◽  
Rating Scale ◽  
Quantitative Polymerase Chain Reaction ◽  
Balloon Catheter ◽  
Traumatic Spinal Cord Injury ◽  
Sprague Dawley ◽  
Time Points ◽  
Cord Injury

In this experimental animal study, we examined alterations in the degree of transcription of two microRNAs (miRs)—miR-21 and -223—in a Sprague-Dawley (SD) rat model of traumatic spinal cord injury (TSCI). Depending on the volume of the balloon catheter (V), a total of 75 male SD rats were divided into the three experimental groups: the sham group (n = 25; V = 0 μL), the mild group (n = 25; V = 20 μL), and the severe group (n = 25; V = 50 μL). Successful induction of TSCI was confirmed on both locomotor rating scale at 4 h and 1, 3 and 7 days post-lesion and histopathologic examinations. Then, RNA isolation and quantitative polymerase chain reaction (PCR) were performed. No differences in the level of miR-21 expression were found at the first time point studied (4 h post-lesion) between the three experimental groups, whereas such differences were significant at all the other time points (p < 0.05). Moreover, there were significant alterations in the level of miR-223 expression at all time points studied through all the experimental groups (p < 0.05). Furthermore, locomotor rating scale scores had a linear relationship with the level of miR-21 expression (R2 = 0.4363, Y = 1.661X + 3.096) and that of miR-223 one (R2 = 0.9104, Y = 0.8385X + 2.328). Taken together, we conclude that up-regulation of miR-21 and -223 might be closely associated with progression and the early course of TSCI, respectively.

scholarly journals Effects of MicroRNA-494 on Astrocyte Proliferation and Synaptic Remodeling in the Spinal Cord of a Rat Model of Chronic Compressive Spinal Cord Injury by Regulating the Nogo/Ngr Signaling Pathway

2018 ◽  
Vol 48 (3) ◽  
pp. 919-933 ◽  
Author(s):  
Yuan Wang ◽  
Jing-Chuan Sun ◽  
Hai-Bo Wang ◽  
Xi-Ming Xu ◽  
Yong Yang ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Signaling Pathway ◽  
Motor Neurons ◽  
Rat Model ◽  
Target Genes ◽  
Quantitative Polymerase Chain Reaction ◽  
Astrocyte Proliferation ◽  
Synaptic Remodeling ◽  
Cord Injury

Background/Aims: Chronic compression of the spinal cord causes the loss of motor neurons in the anterior horn, but the precise and extensive mechanism for the loss is not completely determined. Therefore, this study aims to explore the role of microRNA-494 (miR-494) in the proliferation of astrocytes and in the synaptic remodeling in the spinal cord of a rat model of chronic spinal cord injury (SCI) by regulating the Nogo/NgR signaling pathway. Methods: A rat model of chronic, compressive SCI was established, and the spinal cord state, blood supply changes, and astrocyte apoptosis were observed. Reverse transcription quantitative polymerase chain reaction (RT-qPCR) and Western blotting were used to detect expression of miR-494 and the Nogo/NgR signaling pathway-related genes. Fluorescence in situ hybridization (FISH) was used for detecting miR-494 expression and distribution. Results: Higher miR-494 expression was accompanied by the inhibition of astrocyte proliferation and synaptic remodeling. In addition, CDK6 could be regulated by miR-494 and was shown to be one of the target genes of miR-494. Positive expression of miR-494 detected by FISH was consistent with the results from RT-qPCR that miR-494 could downregulate CDK6 gene expression. Moreover, the direct miR-494 target CDK6 plays important inhibitory roles in chronic SCI by suppressing the Nogo/ NgR signaling pathway. Conclusions: The results demonstrated that miR-494 inhibition can promote astrocyte proliferation and synaptic remodeling by suppressing the Nogo/NgR signaling pathway in a rat model of chronic SCI.

scholarly journals Multi-pronged neuromodulation intervention engages the residual motor circuitry to facilitate walking in a rat model of spinal cord injury

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Marco Bonizzato ◽  
Nicholas D. James ◽  
Galyna Pidpruzhnykova ◽  
Natalia Pavlova ◽  
Polina Shkorbatova ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Rat Model ◽  
Stress Responses ◽  
Learning Algorithm ◽  
Lumbar Spinal Cord ◽  
Cord Injury ◽  
Potential Synergy ◽  
Lumbar Spinal ◽  
Deep Brain

AbstractA spinal cord injury usually spares some components of the locomotor circuitry. Deep brain stimulation (DBS) of the midbrain locomotor region and epidural electrical stimulation of the lumbar spinal cord (EES) are being used to tap into this spared circuitry to enable locomotion in humans with spinal cord injury. While appealing, the potential synergy between DBS and EES remains unknown. Here, we report the synergistic facilitation of locomotion when DBS is combined with EES in a rat model of severe contusion spinal cord injury leading to leg paralysis. However, this synergy requires high amplitudes of DBS, which triggers forced locomotion associated with stress responses. To suppress these undesired responses, we link DBS to the intention to walk, decoded from cortical activity using a robust, rapidly calibrated unsupervised learning algorithm. This contingency amplifies the supraspinal descending command while empowering the rats into volitional walking. However, the resulting improvements may not outweigh the complex technological framework necessary to establish viable therapeutic conditions.

scholarly journals A Collagen-Based Scaffold for Promoting Neural Plasticity in a Rat Model of Spinal Cord Injury

Polymers ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 2245
Author(s):  
Jue-Zong Yeh ◽  
Ding-Han Wang ◽  
Juin-Hong Cherng ◽  
Yi-Wen Wang ◽  
Gang-Yi Fan ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Rat Model ◽  
Neural Plasticity ◽  
Collagen Scaffold ◽  
Glial Scar ◽  
Beneficial Effects ◽  
Cord Injury

In spinal cord injury (SCI) therapy, glial scarring formed by activated astrocytes is a primary problem that needs to be solved to enhance axonal regeneration. In this study, we developed and used a collagen scaffold for glial scar replacement to create an appropriate environment in an SCI rat model and determined whether neural plasticity can be manipulated using this approach. We used four experimental groups, as follows: SCI-collagen scaffold, SCI control, normal spinal cord-collagen scaffold, and normal control. The collagen scaffold showed excellent in vitro and in vivo biocompatibility. Immunofluorescence staining revealed increased expression of neurofilament and fibronectin and reduced expression of glial fibrillary acidic protein and anti-chondroitin sulfate in the collagen scaffold-treated SCI rats at 1 and 4 weeks post-implantation compared with that in untreated SCI control. This indicates that the collagen scaffold implantation promoted neuronal survival and axonal growth within the injured site and prevented glial scar formation by controlling astrocyte production for their normal functioning. Our study highlights the feasibility of using the collagen scaffold in SCI repair. The collagen scaffold was found to exert beneficial effects on neuronal activity and may help in manipulating synaptic plasticity, implying its great potential for clinical application in SCI.

scholarly journals The Therapeutic Potential of Conditioned Medium from Human Breast Milk Stem Cells in Treating Spinal Cord Injury

2020 ◽  
Vol 14 (2) ◽  
pp. 131-138 ◽  
Author(s):  
Maryam Borhani-Haghighi ◽  
Shadan Navid ◽  
Yousef Mohamadi
Keyword(s):  
Spinal Cord ◽  
Stem Cells ◽  
Spinal Cord Injury ◽  
Breast Milk ◽  
Conditioned Medium ◽  
Rat Model ◽  
Intrathecal Administration ◽  
Human Breast Milk ◽  
Human Breast ◽  
Cord Injury

Study Design: Experimental animal study.Purpose: This study investigated the therapeutic effects of human breast milk stem cell (BMSC)-conditioned medium (BMSC-CM) in a model of spinal cord injury (SCI) in male Sprague-Dawley rats.Overview of Literature: SCI is one of the leading causes of disability in addition to sensory and motor impairment. So far, there have been no successful treatments for SCI. Given the positive outcomes associated with using stem cells and their derivatives as a treatment for various diseases, there is a growing interest in using them as an SCI treatment. Recent research has demonstrated that CM from stem cells has therapeutic advantages.Methods: Human BMSCs were isolated and characterized, and CM was subsequently collected. Animals received an intrathecal administration of BMSC-CM after SCI. The activity of caspase-3 was measured to assess apoptosis, and levels of tumor necrosis factor-α and interleukin-1β were measured to assess inflammation. Also, sensory and locomotor performances were assessed after SCI and BMSC-CM administration.Results: Administration of CM from BMSC reduced apoptosis and inflammation at the site of injury in a rat model of SCI (p<0.05). Motor, sensory, locomotor, and sensorimotor performances were significantly improved in rats that received BMSC-CM after SCI.Conclusions: Intrathecal administration of BMSC-CM improved recovery in a rat model of SCI.

scholarly journals Amount of Torque and Duration of Stretching Affects Correction of Knee Contracture in a Rat Model of Spinal Cord Injury

2013 ◽  
Vol 471 (11) ◽  
pp. 3626-3636 ◽  
Author(s):  
Hideki Moriyama ◽  
Yoshiko Tobimatsu ◽  
Junya Ozawa ◽  
Nobuhiro Kito ◽  
Ryo Tanaka
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Rat Model ◽  
Cord Injury ◽  
Knee Contracture
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