scholarly journals Assessment of neuroprotective role of PPAR-gamma agonist in spinal cord injury as possible therapeutic agents

2018 ◽  
Vol 2 (3) ◽  
pp. 251-259
Author(s):  
Zahra Jahanbakhsh ◽  
Hassan Ghoshooni ◽  
Mohammad Taghi Mohammadi
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Oxidative Damage ◽  
Motor Function ◽  
Ppar Gamma ◽  
Control Group ◽  
Injured Spinal Cord ◽  
Histopathological Changes ◽  
Cord Injury ◽  
Ppar Gamma Agonist

It has been reported that peroxisome proliferator-activated receptor (PPAR)-gamma agonist, pioglitazone, has several beneficial roles in many pathological states of nervous tissues. Then in the present study, we aimed to examine the neuroprotective actions of pioglitazone (PPAR-gamma agonist) on motor function, histopathological changes and oxidative damage during spinal cord injury (SCI) in rats. Twenty-four male Wistar rats were randomly divided into three groups as follows; sham, control injury and pioglitazone-treated injured groups. SCI was performed according to the Ping-Weight Drop (contusion) model in rat. The animals received pioglitazone (3 mg/kg) intraperitoneally at times of 15 min after injury and then each 12 hours for seven days. At day seven after SCI, the malondialdehyde and glutathione levels were assessed using biochemical techniques. Histopathological alterations in injured spinal cord and motor function recovery were also assessed after six weeks. Induction of SCI in control group significantly increased the malondialdehyde levels (56%, P=0.002) and decreased the content of glutathione (39±4 nMol/mL) compared to control group (49±6 nMol/mL). Pioglitazone in treated injured rats significantly decreased the malondialdehyde levels (37%, P=0.018) but not glutathione levels (42±1 nMol/mL) compared to sham group. In addition, pioglitazone noticeably improved the histopathological changes of injured spinal cord but not motor function. Our findings revealed that pioglitazone decreases histopathological changes and oxidative damage of injured spinal cord. However, it is suggested that pioglitazone must be applied at higher doses for improving motor function during SCI.

scholarly journals Mmu-miR-27a-5p Promotes the Polarization of Macrophages to the M2 Phenotype at the Site of Spinal Cord Injury in Mice

2021 ◽  
Author(s):  
Mingkun Yang ◽  
Xiaoqian Dang ◽  
Xu Zhang ◽  
Chuan Liu ◽  
Min He
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Motor Function ◽  
Macrophage Polarization ◽  
Spinal Cord Tissue ◽  
Injured Spinal Cord ◽  
Arginase 1 ◽  
Tnf Α ◽  
Cord Injury ◽  
M2 Phenotype

Abstract BackgroundTo investigate the effect of mmu-miR-27a-5p on macrophage polarization in the injured spinal cord and the recovery of motor function after spinal cord injury (SCI) in mice.MethodsA total of 160 specific-pathogen-free male mice were randomly divided into sham, model, mmu-miR-27a-5p, mmu-miR-27a-5p-negative control (NC) groups, with 40 mice in each group. Hindlimb motor function was assessed using the Basso Mouse scale (BMS) before injury and at 1, 3, 7, and 14 days after surgery. Spinal cord tissue samples were obtained at 1, 3, 7, and 14 days after surgery, and macrophage polarization types were detected by using western blot analysis, immunofluorescence, flow cytometry and RT-qPCR.ResultsThe BMS score in the mmu-miR-27a-5p group was significantly higher than that in the model and mmu-miR-27a-5p-NC groups at 7 and 14 days after SCI (X2=26.45-57.62, P<0.05). No significant changes in the expression of M1 markers IL-1β, TNF-α and M2 markers IL-10, Arginase-1 at each time point in the sham group (P=0.96). The expression of IL-1β and TNF-α was significantly lower, while the expression of IL-10 and Arginase-1 were significantly higher in the mmu-miR-27a-5p group as compared to the model and mmu-miR-27a-5p-NC groups at 7 and 14 days after SCI (P<0.05).ConclusionAdministration of mmu-miR-27a-5p can promote the polarization of macrophages to the M2 phenotype in the injured spinal cord, and improve motor function recovery within 14 days after SCI in mice.

scholarly journals Post–spinal cord injury astrocyte-mediated functional recovery in rats after intraspinal injection of the recombinant adenoviral vectors Ad5-VEGF and Ad5-ANG

2017 ◽  
Vol 27 (1) ◽  
pp. 105-115 ◽  
Author(s):  
Tatyana Povysheva ◽  
Maksim Shmarov ◽  
Denis Logunov ◽  
Boris Naroditsky ◽  
Ilya Shulman ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Motor Function ◽  
Fold Increase ◽  
Adenoviral Vectors ◽  
Control Group ◽  
Cord Injury ◽  
Lateral Sclerosis ◽  
Recovery Of Motor Function ◽  
Intraspinal Injection

OBJECTIVEThe most actively explored therapeutic strategy for overcoming spinal cord injury (SCI) is the delivery of genes encoding molecules that stimulate regeneration. In a mouse model of amyotrophic lateral sclerosis and in preliminary clinical trials in patients with amyotrophic lateral sclerosis, the combined administration of recombinant adenoviral vectors (Ad5-VEGF+Ad5-ANG) encoding the neurotrophic/angiogenic factors vascular endothelial growth factor (VEGF) and angiogenin (ANG) was found to slow the development of neurological deficits. These results suggest that there may be positive effects of this combination of genes in posttraumatic spinal cord regeneration. The objective of the present study was to determine the effects of Ad5-VEGF+Ad5-ANG combination therapy on motor function recovery and reactivity of astrocytes in a rat model of SCI.METHODSSpinal cord injury was induced in adult Wistar rats by the weight-drop method. Rats (n = 51) were divided into 2 groups: the experimental group (Ad5-VEGF+Ad5-ANG) and the control group (Ad5-GFP [green fluorescent protein]). Recovery of motor function was assessed using the Basso, Beattie, and Bresnahan scale. The duration and intensity of infectivity and gene expression from the injected vectors were assessed by immunofluorescent detection of GFP. Reactivity of glial cells was assessed by changes in the number of immunopositive cells expressing glial fibrillary acidic protein (GFAP), S100β, aquaporin 4 (AQP4), oligodendrocyte transcription factor 2, and chondroitin sulfate proteoglycan 4. The level of S100β mRNA expression in the spinal cord was estimated by real-time polymerase chain reaction.RESULTSPartial recovery of motor function was observed 30 days after surgery in both groups. However, Basso, Beattie, and Bresnahan scores were 35.9% higher in the Ad5-VEGF+Ad5-ANG group compared with the control group. Specific GFP signal was observed at distances of up to 5 mm in the rostral and caudal directions from the points of injection. A 1.5 to 2.0–fold increase in the number of GFAP+, S100β+, and AQP4+ cells was observed in the white and gray matter at a distance of up to 5 mm from the center of the lesion site in the caudal and rostral directions. At 30 days after injury, a 2-fold increase in S100β transcripts was observed in the Ad5-VEGF+Ad5-ANG group compared with the control group.CONCLUSIONSIntraspinal injection of recombinant adenoviral vectors encoding VEGF and ANG stimulates functional recovery after traumatic SCI. The increased number of S100β+ astrocytes induced by this approach may be a beneficial factor for maintaining the survival and function of neurons. Therefore, gene therapy with Ad5-VEGF+Ad5-ANG vectors is an effective therapeutic method for SCI treatment.

scholarly journals Therapeutic Stimulation for Restoration of Function After Spinal Cord Injury

Physiology ◽  
2017 ◽  
Vol 32 (5) ◽  
pp. 391-398 ◽  
Author(s):  
Aiva Ievins ◽  
Chet T. Moritz
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Motor Function ◽  
Injured Spinal Cord ◽  
Autonomic Functions ◽  
Bladder Control ◽  
Cellular Environment ◽  
Cord Injury ◽  
Incurable Condition ◽  
Stimulation Of

Paralysis due to spinal cord injury can severely limit motor function and independence. This review summarizes different approaches to electrical stimulation of the spinal cord designed to restore motor function, with a brief discussion of their origins and the current understanding of their mechanisms of action. Spinal stimulation leads to impressive improvements in motor function along with some benefits to autonomic functions such as bladder control. Nonetheless, the precise mechanisms underlying these improvements and the optimal spinal stimulation approaches for restoration of motor function are largely unknown. Finally, spinal stimulation may augment other therapies that address the molecular and cellular environment of the injured spinal cord. The fact that several stimulation approaches are now leading to substantial and durable improvements in function following spinal cord injury provides a new perspectives on the previously “incurable” condition of paralysis.

scholarly journals Effect of fetal cerebellar tissue transplantation on the restoration of hind limb locomotor function in rats with spinal cord injury

2016 ◽  
Vol 4 (2) ◽  
pp. 175-180
Author(s):  
V. Medvediev ◽  
Yu. Senchyk ◽  
N. Draguntsova ◽  
S. Dychko ◽  
V. Tsymbaliuk
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Motor Function ◽  
Hind Limb ◽  
Tissue Transplantation ◽  
Control Group ◽  
Function Recovery ◽  
Cord Injury ◽  
Cerebellar Tissue ◽  
Positive Effect

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.

scholarly journals Study of Effect of Salvianolic Acid B on Motor Function Recovery in Rats with Spinal Cord Injury

2014 ◽  
Vol 2014 ◽  
pp. 1-6 ◽  
Author(s):  
Chong Xun ◽  
Yang Hu ◽  
Ming Lu ◽  
Shouyu Wang ◽  
Decheng Lv
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Motor Function ◽  
Treated Group ◽  
Salvianolic Acid B ◽  
Control Group ◽  
Western Blots ◽  
Salvianolic Acid ◽  
Function Recovery ◽  
Cord Injury

In this study effect of salvianolic acid B was observed on motor function recovery of rats with spinal cord injury. 50 rats were selected and after inducing SCI their recovery under controlled conditions was studied using Sal B and PBS (as control). Both compounds were introduced intraperitoneally in respective groups of traumatic rats at the same time intervals for 28 days. It was observed that Sal B introduced at 5  mg/kg/day resulted in better motor function recovery. BBB score was recorded which increased significantly along with the reduction in cavity area observed by bright field microscopy of tissues, that is, from 1 to 10 and from0.20±0.05 mm2to0.10±0.03 mm2, in Sal B treated group, respectively, compared to PBS group. Statistical analysis was carried out using SPSS software (SPSS, Chicago, IL, USA), values were expressed as mean ± SEM, andPvalue <0.01 was considered significant. Effect of Sal B on expression of NF-kB p65 and IkBαwas studied and OD values of densitometry of western blots were taken. MPO activity was also studied. It was observed that treatment of Sal B significantly reduced the expression of both compounds in Sal B treated group as compared to control group after 28 days of treatment.

A comparison of adenosine A2A agonism and methylprednisolone in attenuating neuronal damage and improving functional outcome after experimental traumatic spinal cord injury in rabbits

2006 ◽  
Vol 4 (1) ◽  
pp. 64-70 ◽  
Author(s):  
David O. Okonkwo ◽  
T. Brett Reece ◽  
Jeffrey J. Laurent ◽  
A. Stewart Hawkins ◽  
Peter I. Ellman ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Motor Function ◽  
Receptor Activation ◽  
Control Group ◽  
Spinal Cord Tissue ◽  
Neuronal Viability ◽  
Time Points ◽  
Cord Injury ◽  
Better Than

Object Steroid agents remain the lone pharmacological treatment in widespread use for acute spinal cord injury (SCI), although their utility remains in dispute in the neurotrauma literature. Adenosine A2A receptor activation with ATL-146e, a selective A2A agonist, has shown potential benefit in treating SCI; however, it has not been compared with the gold standard, methylprednisolone. The authors of this study evaluated ATL-146e and methylprednisolone for their ability to preserve neuronal viability and motor function in experimental SCI. Methods New Zealand White rabbits sustained SCI or sham injury via the Allen weight-drop technique. Ten minutes postinjury, animals received ATL-146e (ATL group, 0.06 μg/kg/min intravenously for 3 hours), methylprednisolone (steroid group, 30 mg/kg intravenously), or saline (trauma control group). Hindlimb motor function was recorded every 12 hours using the Tarlov motor grading scale (0, paralysis–5, normal hop). At 48 hours, fixed spinal cord tissue was evaluated for neuronal viability. Hindlimb motor function in animals treated with ATL-146e was equivalent to that of sham-injured animals and was significantly better than that of trauma control animals at all time points and that of steroid-treated animals at 12 hours (p = 0.05). Motor function in steroid-treated animals was worse than in those given ATL-146e and better than that of trauma control animals at later time points, but was not statistically significant (both p > 0.05). Neuronal viability (measured in neurons/hpf) was significantly higher in both treatment groups compared with the trauma control group (12.1 ± 1.4 neurons/hpf for the ATL and 13.3 ± 1.4 neurons/hpf for the steroid group compared with 7.5 ± 1.5 neurons/hpf for the trauma control group; both p < 0.04). Neuronal viability did not differ among ATL-146e–treated, steroid-treated, and sham-injured groups. Conclusions The use of ATL-146e is at least as effective as methylprednisolone in preserving function and is equivalent to methylprednisolone in preserving the structure of spinal cord tissue after blunt SCI. Adenosine A2A receptor activation may be an effective treatment for acute SCI while avoiding the adverse effects of steroid agents.

Effect of electromyographic biofeedback training on motor function of quadriceps femoris in patients with incomplete spinal cord injury: A randomized controlled trial

2021 ◽  
pp. 1-7
Author(s):  
Yun Guo ◽  
Feng Gao ◽  
Jianjun Li ◽  
Mingliang Yang ◽  
Jun Li ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Physical Therapy ◽  
Motor Function ◽  
Intervention Group ◽  
Quadriceps Femoris ◽  
Control Group ◽  
Thigh Circumference ◽  
Electromyographic Biofeedback ◽  
Cord Injury

BACKGROUND: Electromyographic biofeedback (EMG BF) training is an effective method of promoting motor learning and control in neurorehabilitation, but its effect on quadriceps femoris muscle in individuals with spinal cord injury (SCI) is unknown. OBJECTIVE: The aim of the study was to investigate the therapeutic effect of EMG BF training on motor function of quadriceps femoris in patients with incomplete SCI. METHODS: Thirty-three incomplete paraplegic patients with quadriceps femoris strength ranging grade 1 to grade 3 less than 6 months post-injury were enrolled. Control group (n = 16) received conventional physical therapy to enhance quadriceps femoris strength, while intervention group (n = 17) was treated with conventional physical therapy and EMG BF training. All received treatment once a day for 30 days. Surface electromyograph (sEMG), muscle strength and thigh circumference size were assessed to evaluate motor function of quadriceps femoris. Activities of daily living (ADL) was evaluated by Modified Barthel Index (MBI). All the measures evaluated three times in total. RESULTS: Compared to the control group, intervention group significantly improved on sEMG values and strength of quadriceps femoris (PsEMG <  0.001, Pstrength <  0.05). sEMG values of quadriceps femoris increased earlier than strength of quadriceps femoris in intervention group (Prest = 0.07, Pactive = 0.031). There were no statistical differences in thigh circumference size and ADL scores between groups (Pthigh >  0.05, PADL = 0.423). CONCLUSIONS: EMG BF training appeared to be a useful tool to enhance motor function of quadriceps femoris in patients with incomplete SCI. sEMG could quantify the changes of single muscle myodynamia precisely before visible or touchable changes occur.

Sign in / Sign up

Export Citation Format

Share Document