scholarly journals Exendin-4 Plays a Protective Role in a Rat Model of Spinal Cord Injury Through SERCA2

2018 ◽  
Vol 47 (2) ◽  
pp. 617-629 ◽  
Author(s):  
Zhonglei Sun ◽  
Yingfu Liu ◽  
Xianbin Kong ◽  
Renjie Wang ◽  
Yunqiang Xu ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Rat Model ◽  
Rating Scale ◽  
Protective Role ◽  
Female Rats ◽  
Spinal Cord Tissue ◽  
Cord Injury ◽  
Glucagon Like Peptide 1 ◽  
Long Acting

Background/Aims: Current therapies for spinal cord injury (SCI) have limited efficacy, and identifying a therapeutic target is a pressing need. Sarcoplasmic/endoplasmic reticulum Ca2+ ATPase 2 (SERCA2) plays an important role in regulating calcium homeostasis, which has been shown to inhibit apoptosis. Exendin-4 has been shown to inhibit the apoptosis of nerve cells in SCI, which can also improve SERCA2 expression. In this study, we sought to determine whether exendin-4 plays a protective role in a rat model of SCI via SERCA2. Methods: To investigate the effects of exendin-4 on SCI, a rat model of SCI was induced by a modified version of Allen’s method. Spinal cord tissue sections from rats and western blot analysis were used to examine SERCA2 expression after treatment with the long-acting glucagon-like peptide 1 receptor exendin-4 or the SERCA2 antagonist 5(6)-carboxyfluorescein diacetate N-succinimidyl ester (CE). Locomotor function was evaluated using the Basso Beattie Bresnahan locomotor rating scale and slanting board test. Results: Cell apoptosis was increased with CE treatment and decreased with exendin-4 treatment. Upregulation of SERCA2 in female rats with SCI resulted in an improvement of motor function scores and histological changes. Conclusion: These findings suggest that exendin-4 plays a protective role in a rat model of SCI through SERCA2 via inhibition of apoptosis. Existing drugs targeting SERCA2 may be an effective therapeutic strategy for the treatment of SCI.

Protective role of β-carotene against oxidative stress and neuroinflammation in a rat model of spinal cord injury

2018 ◽  
Vol 61 ◽  
pp. 92-99 ◽  
Author(s):  
Lihui Zhou ◽  
Lian Ouyang ◽  
Shuangzhi Lin ◽  
Song Chen ◽  
YingJie Liu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Rat Model ◽  
Protective Role ◽  
Cord Injury ◽  
Β Carotene

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 The Effect of iPS-Derived Neural Progenitors Seeded on Laminin-Coated pHEMA-MOETACl Hydrogel with Dual Porosity in a Rat Model of Chronic Spinal Cord Injury

2019 ◽  
Vol 28 (4) ◽  
pp. 400-412 ◽  
Author(s):  
Jiri Ruzicka ◽  
Nataliya Romanyuk ◽  
Klara Jirakova ◽  
Ales Hejcl ◽  
Olga Janouskova ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Rat Model ◽  
Experimental Period ◽  
Neural Progenitors ◽  
Sensory Function ◽  
Dual Porosity ◽  
Spinal Cord Tissue ◽  
Cord Injury

Spinal cord injury (SCI), is a devastating condition leading to the loss of locomotor and sensory function below the injured segment. Despite some progress in acute SCI treatment using stem cells and biomaterials, chronic SCI remains to be addressed. We have assessed the use of laminin-coated hydrogel with dual porosity, seeded with induced pluripotent stem cell-derived neural progenitors (iPSC-NPs), in a rat model of chronic SCI. iPSC-NPs cultured for 3 weeks in hydrogel in vitro were positive for nestin, glial fibrillary acidic protein (GFAP) and microtubule-associated protein 2 (MAP2). These cell-polymer constructs were implanted into a balloon compression lesion, 5 weeks after lesion induction. Animals were behaviorally tested, and spinal cord tissue was immunohistochemically analyzed 28 weeks after SCI. The implanted iPSC-NPs survived in the scaffold for the entire experimental period. Host axons, astrocytes and blood vessels grew into the implant and an increased sprouting of host TH+ fibers was observed in the lesion vicinity. The implantation of iPSC-NP-LHM cell-polymer construct into the chronic SCI led to the integration of material into the injured spinal cord, reduced cavitation and supported the iPSC-NPs survival, but did not result in a statistically significant improvement of locomotor recovery.

The Regulation of Bone Morphogenetic Protein/Smads Signaling Pathway in Spinal Cord Injury

2020 ◽  
Vol 10 (3) ◽  
pp. 323-328
Author(s):  
Zhigang Zhou ◽  
Kai Cao ◽  
Jianping Liao ◽  
Song Zhou ◽  
Liangliang Zhou ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Treatment Group ◽  
Signaling Pathway ◽  
Rating Scale ◽  
Enzyme Linked Immunosorbent Assay ◽  
Control Group ◽  
Spinal Cord Tissue ◽  
Cord Injury ◽  
Smad5 Mrna

The incidence of spinal cord injury (SCI) increases year by year. SCI is characterized as high disability rate and poor prognosis. BMP/Smads signaling participates in the formation of osteoblasts and renal failure. This article will explore the regulation of BMP/Smads signaling pathway in SCI. Wistar rats were divided into control group; SCI group; and BMP-2 treatment group that were treated by tail vein injection of BMP-2 antisense oligonucleotide BMP-2 phosphorothioate AODN at 30 min after modeling. Real-time PCR and Western blot were used to detect BMP-2, Smad1, and Smad5 expressions. Hematoxylin-eosin (HE) staining was applied to analyze the change of SCI in each group. Immunohistochemistry (IHC) was selected to test BMPR Ia expression. Basso, Beattie Bresnahan-cocomotor rating scale (BBB) scale and Reuter score were compared. Enzyme-linked immunosorbent assay (ELISA) was adopted to detect TNF-α and Interleukin-2 (IL-2) expressions. Compared with the control group, BMP-2, Smad1, and Smad5 mRNA and protein expressions increased, BBB score declined, Reuter score elevated, and TNF-α and IL-2 secretion enhanced in the SCI group (P < 0.05). HE staining showed spinal cord injury, and IHC exhibited increased expression of BMPR Ia. The TGF-β treatment group significantly reduced the expressions of BMP-2, Smad1, and Smad5 mRNA and protein, increased BBB score, reduced Reuter score, and weakened the secretions of TNF-α and IL-2 (P < 0.05). HE staining demonstrated decreased reduction of spinal cord tissue and declined expression of BMPR Ia. SCI activated BMP/Smads signaling pathway, up-regulated BMPR Ia expression, and promoted inflammation. Regulation of BMP/Smads signaling pathway can downregulate BMPR Ia expression and inhibit inflammation to effectively relieve 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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