scholarly journals Prochlorperazine Withdraws the Delayed Onset Tonic Activity of Unloaded Rat Soleus Muscle: A Pilot Study

Life ◽  
2021 ◽  
Vol 11 (11) ◽  
pp. 1161
Author(s):  
Vitaliy E. Kalashnikov ◽  
Sergey A. Tyganov ◽  
Olga V. Turtikova ◽  
Ekaterina P. Kalashnikova ◽  
Margarita V. Glazova ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Electrical Activity ◽  
Protein Content ◽  
Soleus Muscle ◽  
Hindlimb Suspension ◽  
Lumbar Spinal Cord ◽  
Emg Activity ◽  
Control Group ◽  
Cord Injury ◽  
Rat Soleus Muscle

A gradual increase in rat soleus muscle electromyographic (EMG) activity is known to occur after 3–4 days of hindlimb suspension/unloading (HS). The physiological significance and mechanisms of such activity of motoneurons under unloading conditions are currently unclear. Since hyperactivity of motoneurons and muscle spasticity after spinal cord injury are associated with KCC2 downregulation, we hypothesized that a decrease in potassium (K+)/chloride (Cl−) co-transporter 2 (KCC2) in motoneurons would be responsible for an increase in soleus muscle EMG activity during HS. We aimed to investigate the effect of prochlorperazine (KCC2 activator) on the electrical activity of rat soleus muscle under HS. Wistar rats were divided into the following groups: (1) vivarium control (C), (2) 7-day HS group (7HS) and (3) 7-day HS group plus intraperitoneal injections of prochlorperazine (10 mg/kg, daily) (7HS + P). Expression of proteins in the motoneurons of the lumbar spinal cord was determined by Western blotting. An electromyogram of the rat soleus muscle was recorded using intramuscular electrodes. KCC2 content after 7-day HS significantly decreased by 34% relative to the control group. HS-induced decrease in KCC2 protein content was prevented by prochlorperazine administration. HS also induced a significant 80% decrease in KCC2 Ser940 phosphorylation; however prochlorperazine did not affect KCC2 phosphorylation. The treatment of the rats with prochlorperazine prevented a HS-induced increase in Na(+)/K(+)/(Cl−) co-transporter 1 (KCC2 antagonist) protein content. In parallel with the restoration of KCC2 content, prochlorperazine administration during HS partially prevented an increase in the soleus muscle tonic EMG activity. Thus, prochlorperazine administration during 7-day HS prevents a decrease in KCC2 protein expression in motoneurons and significantly reduces the level of HS-induced soleus muscle electrical activity.

scholarly journals Contusion spinal cord injury upregulates p53 protein expression in rat soleus muscle at multiple timepoints but not key senescence cytokines

2020 ◽  
Vol 8 (3) ◽  
Author(s):  
Zachary A. Graham ◽  
Abigail Goldberger ◽  
Daniella Azulai ◽  
Christine F. Conover ◽  
Fan Ye ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Protein Expression ◽  
Soleus Muscle ◽  
P53 Protein ◽  
P53 Protein Expression ◽  
Cord Injury ◽  
Rat Soleus Muscle

PROTECTIVE EFFECT OF SOME SALTS 2-AMINOETHANESULFONIC ACID IN AN EXPERIMENTAL MODEL OF DEGENERATIVE SPINAL CORD INJURY

2020 ◽  
pp. 41-47
Author(s):  
Semeleva E.V. ◽  
Blinova E.V. ◽  
Zaborovsky A.V. ◽  
Vasilkina O.V. ◽  
Shukurov A.S.
Keyword(s):  
Spinal Cord ◽  
Morphological Changes ◽  
Male Rats ◽  
Zinc Salt ◽  
Control Group ◽  
Morphological Studies ◽  
Cord Injury ◽  
The Central Nervous System ◽  
Acid Compound ◽  
Lateral Sclerosis

In this work, we studied the pharmacological activity of zinc and magnesium salts of 2-aminoethanesulfonic acid in white non-linear male rats with amyotrophic lateral sclerosis, which was modeled by neurotoxicantsimplication into the pelvic part of spinal cord. After the reproduction of the pathology in animals, the indices of motor activity were recorded in the Rotarod test, and morphological studies of spinal cord sections stained according to Nisl in the Belshovsky modification were carried out. It was shown that the magnesium salt of 2-aminoethanesulfonic acid (compound LHT-317) to a greater extent reduces the development of motor disorders in experimental animals compared with the control group on the 4th day of observation. The course of intravenous administration of the studied compounds of 2-aminoethanesulfonic acid did not inhibit morphological changes in the spinal cord that develop in degenerative-dystrophic pathology of the central nervous system: connections. Moreover, if, against the background of treatment with zinc salt, the total area of motor zones in animals of the experimental group exceeded that of control rats, then the number of motoneurons did not differ from the control.

scholarly journals Exercise Ameliorates Spinal Cord Injury by Changing DNA Methylation

Cells ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 143
Author(s):  
Ganchimeg Davaa ◽  
Jin Young Hong ◽  
Tae Uk Kim ◽  
Seong Jae Lee ◽  
Seo Young Kim ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Motor Cortex ◽  
Functional Recovery ◽  
Treadmill Exercise ◽  
Exercise Group ◽  
Control Group ◽  
Epigenetic Changes ◽  
Cord Injury ◽  
The Brain

Exercise training is a traditional method to maximize remaining function in patients with spinal cord injury (SCI), but the exact mechanism by which exercise promotes recovery after SCI has not been identified; whether exercise truly has a beneficial effect on SCI also remains unclear. Previously, we showed that epigenetic changes in the brain motor cortex occur after SCI and that a treatment leading to epigenetic modulation effectively promotes functional recovery after SCI. We aimed to determine how exercise induces functional improvement in rats subjected to SCI and whether epigenetic changes are engaged in the effects of exercise. A spinal cord contusion model was established in rats, which were then subjected to treadmill exercise for 12 weeks. We found that the size of the lesion cavity and the number of macrophages were decreased more in the exercise group than in the control group after 12 weeks of injury. Immunofluorescence and DNA dot blot analysis revealed that levels of 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) in the brain motor cortex were increased after exercise. Accordingly, the expression of ten-eleven translocation (Tet) family members (Tet1, Tet2, and Tet3) in the brain motor cortex also elevated. However, no macrophage polarization was induced by exercise. Locomotor function, including Basso, Beattie, and Bresnahan (BBB) and ladder scores, also improved in the exercise group compared to the control group. We concluded that treadmill exercise facilitates functional recovery in rats with SCI, and mechanistically epigenetic changes in the brain motor cortex may contribute to exercise-induced improvements.

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 AAV2-mediated and hypoxia response element-directed expression of bFGF in neural stem cells showed therapeutic effects on spinal cord injury in rats

2021 ◽  
Vol 12 (3) ◽  
Author(s):  
Sipin Zhu ◽  
Yibo Ying ◽  
Jiahui Ye ◽  
Min Chen ◽  
Qiuji Wu ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Clinical Trials ◽  
Control Group ◽  
Therapeutic Effects ◽  
Hypoxia Response Element ◽  
Neurofilament Protein ◽  
Response Element ◽  
Hypoxia Response ◽  
Cord Injury

AbstractNeural stem cell (NSCs) transplantation has been one of the hot topics in the repair of spinal cord injury (SCI). Fibroblast growth factor (FGF) is considered a promising nerve injury therapy after SCI. However, owing to a hostile hypoxia condition in SCI, there remains a challenging issue in implementing these tactics to repair SCI. In this report, we used adeno-associated virus 2 (AAV2), a prototype AAV used in clinical trials for human neuron disorders, basic FGF (bFGF) gene under the regulation of hypoxia response element (HRE) was constructed and transduced into NSCs to yield AAV2-5HRE-bFGF-NSCs. Our results showed that its treatment yielded temporally increased expression of bFGF in SCI, and improved scores of functional recovery after SCI compared to vehicle control (AAV2-5HRE-NSCs) based on the analyses of the inclined plane test, Basso–Beattie–Bresnahan (BBB) scale and footprint analysis. Mechanistic studies showed that AAV2-5HRE-bFGF-NSCs treatment increased the expression of neuron-specific neuronal nuclei protein (NeuN), neuromodulin GAP43, and neurofilament protein NF200 while decreased the expression of glial fibrillary acidic protein (GFAP) as compared to the control group. Further, the expressions of autophagy-associated proteins LC3-II and Beclin 1 were decreased, whereas the expression of P62 protein was increased in AAV2-5HRE-bFGF-NSCs treatment group. Taken together, our data indicate that AAV2-5HRE-bFGF-NSCs treatment improved the recovery of SCI rats, which is accompanied by evidence of nerve regeneration, and inhibition of SCI-induced glial scar formation and cell autophagy. Thus, this study represents a step forward towards the potential use of AAV2-5HRE-bFGF-NSCs for future clinical trials of SCI repair.

scholarly journals Effect of pelvic laparoscopic implantation of neuroprosthesis in spinal cord injured subjects: a 1-year prospective randomized controlled study

Spinal Cord ◽  
2021 ◽  
Author(s):  
Helge Kasch ◽  
Uffe Schou Løve ◽  
Anette Bach Jønsson ◽  
Kaare Eg Severinsen ◽  
Marc Possover ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Outcome Measures ◽  
Outcome Measure ◽  
Secondary Outcome ◽  
Controlled Study ◽  
Control Group ◽  
Walking Ability ◽  
Data Set ◽  
Cord Injury

Abstract Study design 1-year prospective RCT. Objective Examine the effect of implantable pulse generator and low-frequency stimulation of the pelvic nerves using laparoscopic implantation of neuroprosthesis (LION) compared with neuromuscular electrical stimulation (NMES) in SCI. Methods Inclusion criteria: traumatic spinal cord injury (SCI), age 18–55 years, neurological level-of-injury Th4–L1, time-since-injury >1 year, and AIS-grades A–B. Participants were randomized to (A) LION procedure or (B) control group receiving NMES. Primary outcome measure: Walking Index for Spinal Cord Injury (WISCI-II), which is a SCI specific outcome measure assessing ability to ambulate. Secondary outcome measures: Spinal Cord Independence Measure III (SCIM III), Patient Global Impression of Change (PGIC), Penn Spasm Frequency Scale (PSFS), severity of spasticity measured by Numeric Rating Scale (NRS-11); International Spinal Cord Injury data sets-Quality of Life Basic Data Set (QoLBDS), and Brief Pain Inventory (BPI). Results Seventeen SCI individuals, AIS grade A, neurological level ranging from Th4–L1, were randomized to the study. One individual was excluded prior to intervention. Eight participants (7 males) with a mean age (SD) of 35.5 (12.4) years were allocated to the LION procedure, 8 participants (7 males) with age of 38.8 (15.1) years were allocated to NMES. Significantly, 5 LION group participants gained 1 point on the WISCI II scale, (p < 0.013; Fisher´s exact test). WISCI II scale score did not change in controls. No significant changes were observed in the secondary outcome measures. Conclusion The LION procedure is a promising new treatment for individuals with SCI with significant one-year improvement in walking ability.

Neuroprotective effects of granulocyte colony-stimulating factor and relationship to promotion of angiogenesis after spinal cord injury in rats

2011 ◽  
Vol 15 (4) ◽  
pp. 414-421 ◽  
Author(s):  
Junko Kawabe ◽  
Masao Koda ◽  
Masayuki Hashimoto ◽  
Takayuki Fujiyoshi ◽  
Takeo Furuya ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Treated Group ◽  
Control Group ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Neuroprotective Effects ◽  
Cord Injury ◽  
Bone Marrow Derived Cells ◽  
Stimulating Factor ◽  
Angiogenic Cytokines

Object Granulocyte colony-stimulating factor (G-CSF) has neuroprotective effects on the CNS. The authors have previously demonstrated that G-CSF also exerts neuroprotective effects in experimental spinal cord injury (SCI) by enhancing migration of bone marrow–derived cells into the damaged spinal cord, increasing glial differentiation of bone marrow–derived cells, enhancing antiapoptotic effects on both neurons and oligodendrocytes, and by reducing demyelination and expression of inflammatory cytokines. Because the degree of angiogenesis in the subacute phase after SCI correlates with regenerative responses, it is possible that G-CSF's neuroprotective effects after SCI are due to enhancement of angiogenesis. The aim of this study was to assess the effects of G-CSF on the vascular system after SCI. Methods A contusive SCI rat model was used and the animals were randomly allocated to either a G-CSF–treated group or a control group. Integrity of the blood–spinal cord barrier was evaluated by measuring the degree of edema in the cord and the volume of extravasation. For histological evaluation, cryosections were immunostained with anti–von Willebrand factor and the number of vessels was counted to assess revascularization. Real-time reverse transcriptase polymerase chain reaction was performed to assess expression of angiogenic cytokines, and recovery of motor function was assessed with function tests. Results In the G-CSF–treated rats, the total number of vessels with a diameter > 20 μm was significantly larger and expression of angiogenic cytokines was significantly higher than those in the control group. The G-CSF–treated group showed significantly greater recovery of hindlimb function than the control group. Conclusions These results suggest that G-CSF exerts neuroprotective effects via promotion of angiogenesis after SCI.

The Effect of Acceptance and Commitment Therapy on Psychological Flexibility and Emotional Regulation in Patients with Spinal Cord Injuries: A Randomized Controlled Trial

2021 ◽  
Vol In Press (In Press) ◽  
Author(s):  
Mohammad Saeed Khanjani ◽  
Javad Kazemi ◽  
Jalal Younesi ◽  
Asghar Dadkhah ◽  
Akbar Biglarian ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Emotion Regulation ◽  
Emotional Regulation ◽  
Spinal Cord Injuries ◽  
Psychological Flexibility ◽  
Control Group ◽  
Acceptance And Commitment ◽  
Significant Difference ◽  
Cord Injury ◽  
And Control

Background: Patients with spinal cord injuries suffer from some psychological problems, such as inadequate emotional regulation and flexibility for adapting to the post-injury condition. In this regard, acceptance and commitment therapy (ACT) can improve psychological flexibility and emotional regulation. Objectives: The main goal of this study was to analyze the effectiveness of ACT in improving psychological flexibility and emotional regulation in patients with spinal cord injuries. Methods: This quasi-experimental design study was based on a pretest-posttest method with a control group. The study population consisted of all patients with spinal cord injury referred to Jalaeipour Rehabilitation Center in Tehran. The study sample included 30 patients with spinal cord injury selected by the purposive sampling method. The inclusion criteria were patients aged 20 to 55 years, residing in Tehran, and with at least a high school diploma. The injury duration varied between one and five years, and the injuries were thoracic and lumbar injuries and an intermediate score of psychological flexibility and emotion regulation. The exclusion criteria were patients with cervical spinal cord injuries, as well as patients who were simultaneously receiving another psychological treatment together with the subjects who suffered from brain damage. Patients were randomly assigned to the experimental and control groups based on random numbers. There were 15 patients in each group. The intervention group received ACT during eight sessions (1.5-hour group therapy) held once a week at Jalaeipour Rehabilitation Center in Tehran (2018), while the control group received routine care. Dennis and Vander Wal’s cognitive flexibility inventory (CFI) and Gross and John’s emotion regulation questionnaire (ERQ) were completed before and one week after the intervention. The data were analyzed using multivariate analysis of covariance (MANCOVA). Results: There was a significant difference in demographic indicators between the two groups. Based on MANCOVA with the baseline score, the mean scores of psychological flexibility and emotion regulation had a significant difference regarding the results of ACT between the experimental and control groups (P < 0.05). Conclusions: According to the findings, ACT can improve psychological flexibility and emotional regulation in patients with spinal cord injuries.

Time-dependent progression of neurogenic lower urinary tract dysfunction after spinal cord injury in the mouse model

2021 ◽  
Author(s):  
Tetsuichi Saito ◽  
Daisuke Gotoh ◽  
Naoki Wada ◽  
Pradeep Tyagi ◽  
Tomonori Minagawa ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Time Course ◽  
Time Dependent ◽  
Lower Urinary Tract Dysfunction ◽  
Emg Activity ◽  
Mrna Levels ◽  
Mechanosensitive Channels ◽  
Reduction Time ◽  
Cord Injury

This study evaluated the time-course changes in bladder and external urinary sphincter (EUS) activity as well as the expression of mechanosensitive channels in lumbosacral dorsal root ganglia (DRG) after spinal cord injury (SCI). Female C57BL/6N mice in the SCI group underwent transection of the Th8/9 spinal cord. Spinal intact mice and SCI mice at 2, 4 and 6 weeks post SCI were evaluated by single-filling cystometry and EUS-electromyography (EMG). In another set of mice, the bladder and L6-S1 DRG were harvested for protein and mRNA analyses. In SCI mice, non-voiding contractions was confirmed at 2 weeks post-SCI, and did not increase over time to 6 weeks. In 2-weeks SCI mice, EUS-EMG measurements revealed detrusor-sphincter dyssynergia (DSD), but periodic EMG reductions during bladder contraction were hardly observed. At 4 weeks, SCI mice showed increases of EMG activity reduction time with increased voiding efficiency (VE). At 6 weeks, SCI mice exhibited a further increase in EMG reduction time. RT-PCR of L6-S1 DRG showed increased mRNA levels of TRPV1 and ASIC1-3 in SCI mice with a decrease of ASIC2-3 at 6 weeks compared to 4 weeks whereas Piezo2 showed a slow increase at 6 weeks. Protein assay showed the SCI-induced overexpression of bladder BDNF with a time-dependent decrease post SCI. These results indicate that detrusor overactivity is established in the early phase whereas DSD is completed later at 4 weeks with an improvement at 6 weeks post SCI, and that mechanosensitive channels may be involved in the time-dependent changes.

Transplantation of Neural Stem/Progenitor Cells at Different Locations in Mice with Spinal Cord Injury

2014 ◽  
Vol 23 (11) ◽  
pp. 1451-1464 ◽  
Author(s):  
Hiroki Iwai ◽  
Satoshi Nori ◽  
Soraya Nishimura ◽  
Akimasa Yasuda ◽  
Morito Takano ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Progenitor Cells ◽  
Functional Recovery ◽  
Control Group ◽  
Cord Injury ◽  
Neural Stem Progenitor Cells ◽  
Neurotropic Factor ◽  
Transplantation Site

Transplantation of neural stem/progenitor cells (NS/PCs) promotes functional recovery after spinal cord injury (SCI); however, few studies have examined the optimal site of NS/PC transplantation in the spinal cord. The purpose of this study was to determine the optimal transplantation site of NS/PCs for the treatment of SCI. Wild-type mice were generated with contusive SCI at the T10 level, and NS/PCs were derived from fetal transgenic mice. These NS/PCs ubiquitously expressed ffLuc-cp156 protein (Venus and luciferase fusion protein) and so could be detected by in vivo bioluminescence imaging 9 days postinjury. NS/PCs (low: 250,000 cells per mouse; high: 1 million cells per mouse) were grafted into the spinal cord at the lesion epicenter (E) or at rostral and caudal (RC) sites. Phosphate-buffered saline was injected into E as a control. Motor functional recovery was better in each of the transplantation groups (E-Low, E-High, RC-Low, and RC-High) than in the control group. The photon counts of the grafted NS/PCs were similar in each of the four transplantation groups, suggesting that the survival of NS/PCs was fairly uniform when more than a certain threshold number of cells were transplanted. Quantitative RT-PCR analyses demonstrated that brain-derived neurotropic factor expression was higher in the RC segment than in the E segment, and this may underlie why NS/PCs more readily differentiated into neurons than into astrocytes in the RC group. The location of the transplantation site did not affect the area of spared fibers, angiogenesis, or the expression of any other mediators. These findings indicated that the microenvironments of the E and RC sites are able to support NS/PCs transplanted during the subacute phase of SCI similarly. Optimally, a certain threshold number of NS/PCs should be grafted into the E segment to avoid damaging sites adjacent to the lesion during the injection procedure.

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