scholarly journals Effect of exogenous leukemia inhibitory factor on reparative regeneration of the peripheral nerve in mice

2017 ◽  
Vol 5 (2) ◽  
pp. 182-187
Author(s):  
I. Labunets ◽  
A. Demydchuk ◽  
S. Shamalo ◽  
N. Utko ◽  
A. Rodnichenko ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Sciatic Nerve ◽  
Glutathione Peroxidase ◽  
Peripheral Nerve ◽  
Nerve Injury ◽  
Motor Function ◽  
Leukemia Inhibitory Factor ◽  
Nerve Fibers ◽  
Reparative Regeneration ◽  
The Right

The role of trophic and growth factors in the regeneration of the damaged peripheral nerve is known. The leukemia inhibitory factor (LIF) exhibits properties not only of the polyfunctional cytokine, but also the neurotrophic factor. Regeneration of the peripheral nerve is impaired during oxidative stress in the area of injury.The purpose of the work was to investigate the effect of recombinant human LIF (rhLIF) on the efficacy of reparative regeneration of the sciatic nerve.Materials and methods. Adult male FVB/N mice were divided into the following groups: sham-operated; trauma (neurotomy) of the right sciatic nerve; nerve injury and subcutaneous injection of rhLIF at a dose of 1 μg per animal daily from the third day after the nerve injury. The study was conducted 4 weeks after the injury. At morphometry, the density of nerve fibers in distal nerve segments after impregnation with nitric oxide silver was evaluated. The motor function was evaluated in the “open field” test by the number of crossed squares, and in footprint test by the distance between the extreme toes of the right foot. In the area of muscle injury, the content of malondialdehyde, superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase was estimated.Results. The total number of nerve fibers in the distal segment of the nerve of mice with trauma and injection of rhLIF is greater (p < 0.05) than in mice with only nerve injury and does not differ from sham-operated animals. Horizontal motor activity in mice with nerve injury is lower (p <0.05) than in sham-operated and cytokine injected mice. The distance between the extreme toes of the sham-operated mice is greater (p < 0.05) than in mice with nerve injury, as well as injuries and injections of rhLIF, but after the injection of cytokine, the rates are higher (p < 0.05) than in the group of mice without it. After the injury, the content of malondialdehyde and catalase activity increases in muscle tissue, while the activity of glutathione reductase decreases (p < 0.05). Under the influence of rhLIF, the parameters change to the values of sham-operated mice, and, in addition, the activity of the glutathione peroxidase is significantly increased.Conclusions. Injection of rhLIF to mice with a sciatic nerve injury promotes a more complete restoration of the structural organization of the damaged nerve and improves the motor function of the injured limb. At the same time, the balance between the factors of oxidative stress and antioxidant system is improved in the muscle tissue in the area of the nerve injury.

scholarly journals Ferula asafoetida Linn. is effective for early functional recovery following mechanically induced insult to the sciatic nerve of a mouse model

2020 ◽  
Vol 19 (9) ◽  
pp. 1903-1910
Author(s):  
Syed Kashif Shahid Kamran ◽  
Azhar Rasul ◽  
Haseeb Anwar ◽  
Shahzad Irfan ◽  
Khizar Sami Ullah ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Sciatic Nerve ◽  
Antioxidant Capacity ◽  
Grip Strength ◽  
Nerve Injury ◽  
Muscle Mass ◽  
Motor Function ◽  
Sciatic Nerve Injury ◽  
Sensory Function ◽  
Ferula Asafoetida

Purpose: To evaluate the effect of Ferula asafoetida (oleo gum resin powder) on sensory and motor functions retrieval on an induced sciatic nerve injury in a mouse model.Methods: A mechanical crush was inserted in the sciatic nerve of all the experimental mice after acclimatization. The mice were allocated to four groups; one normal chow group (control, n = 7) and three Ferula asafoetida chow groups (each n = 7) of different doses (50, 100 and 200 mg/kg). Muscle grip strength, muscle mass, and sciatic functional index were measured to evaluate the motor function regain, while sensory function regain was assessed by hot plate test. Oxidative stress and glycemic levels were measured by biochemical assays.Results: The findings of this study indicate that Ferula asafoetida 200 mg/kg has a highly significant (p≤ 0.001) ameliorating effect in terms of improved grip strength (77.7 ± 5.4 % for 200 mg/kg vs. 46 ± 5.1 % for control), reversal of SFI towards normal ( -34 ± 8.1 for 200 mg/kg group vs. –61 ± 6.1 for control), decrease in paw withdrawal latency (7.10 ± 0.06 s for 200 mg/kg group vs. 15 ± 0.5 s for control) on day 12 post-injury, as well as restoration of skeletal muscle mass towards normal. Interestingly, F. asafoetida chow 50 mg/kg and 100 mg/kg groups also impacted significant (p < 0.01) improvement in the ameliorative effect. However, the differences among all treatment groups in ameliorating recovery were not significant (p > 0.05). Moreover, comparatively improved (p < 0.0001) total antioxidant capacity along with reduced total oxidant status (p = 0.01) in the Ferula asafoetida chow (200 mg/kg) group, indicate the antioxidative effect of this plant. Furthermore, the treated mice (200 mg/kg) also expressedan improved glycemic level (p = 0.0005).Conclusion: Ferula asafoetida supplementation helps to accelerate both sensory and motor function retrieval following sciatic nerve injury. This  improvement is thought to be correlated with the antioxidant capacity of the plant. However, further investigations are required to identify the therapeutic principles responsible for the observed actions. Keywords: Sciatic nerve injury, Ferula asafoetida, Function recovery, Oxidative stress, Biochemical analysis

scholarly journals Nogo-C Inhibits Peripheral Nerve Regeneration by Regulating Schwann Cell Apoptosis and Dedifferentiation

2021 ◽  
Vol 14 ◽  
Author(s):  
Bo Jia ◽  
Wei Huang ◽  
Yu Wang ◽  
Peng Zhang ◽  
Zhiwei Wang ◽  
...  
Keyword(s):  
Sciatic Nerve ◽  
Schwann Cell ◽  
Peripheral Nerve ◽  
Nerve Regeneration ◽  
Schwann Cells ◽  
Nerve Injury ◽  
Cell Apoptosis ◽  
Peripheral Nerve Regeneration ◽  
Nerve Fibers ◽  
Cell Dedifferentiation

While Nogo protein demonstrably inhibits nerve regeneration in the central nervous system (CNS), its effect on Schwann cells in peripheral nerve repair and regeneration following sciatic nerve injury remains unknown. In this research, We assessed the post-injury expression of Nogo-C in an experimental mouse model of sciatic nerve-crush injury. Nogo-C knockout (Nogo-C–/–) mouse was generated to observe the effect of Nogo-C on sciatic nerve regeneration, Schwann cell apoptosis, and myelin disintegration after nerve injury, and the effects of Nogo-C on apoptosis and dedifferentiation of Schwann cells were observed in vitro. We found that the expression of Nogo-C protein at the distal end of the injured sciatic nerve increased in wild type (WT) mice. Compared with the injured WT mice, the proportion of neuronal apoptosis was significantly diminished and the myelin clearance rate was significantly elevated in injured Nogo-C–/– mice; the number of nerve fibers regenerated and the degree of myelination were significantly elevated in Nogo-C–/– mice on Day 14 after injury. In addition, the recovery of motor function was significantly accelerated in the injured Nogo-C–/– mice. The overexpression of Nogo-C in primary Schwann cells using adenovirus-mediated gene transfer promoted Schwann cells apoptosis. Nogo-C significantly reduced the ratio of c-Jun/krox-20 expression, indicating its inhibition of Schwann cell dedifferentiation. Above all, we hold the view that the expression of Nogo-C increases following peripheral nerve injury to promote Schwann cell apoptosis and inhibit Schwann cell dedifferentiation, thereby inhibiting peripheral nerve regeneration.

scholarly journals An Investigation into the Rehabilitative Mechanism of Tuina in the Treatment of Sciatic Nerve Injury

2020 ◽  
Vol 2020 ◽  
pp. 1-11
Author(s):  
Taotao Lv ◽  
Yanjun Mo ◽  
Tianyuan Yu ◽  
Yumo Zhang ◽  
Shuai Shao ◽  
...  
Keyword(s):  
Sciatic Nerve ◽  
Peripheral Nerve ◽  
Nerve Injury ◽  
Myelin Sheath ◽  
Peripheral Nerve Injury ◽  
Sham Group ◽  
Sciatic Nerve Injury ◽  
Ultrastructural Changes ◽  
Rna Seq ◽  
The Right

Objective. To explore the effect of tuina on the gene expression at the point of nerve injury in rats with sciatic nerve injury (SNI) and to elucidate the repair mechanism of tuina promoting the functional recovery of peripheral nerve injury. Methods. In the Sham group, the right sciatic nerve was exposed without clamping. The SNI model was established using the sciatic nerve clamp method on the right leg and then randomly divided into the SNI group and the Tuina group. Seven days after modeling, the Tuina group was treated daily with a “massage and tuina manipulation simulator” (Patent No. ZL 2007 0187403.1), which was used daily to stimulate Yinmen (BL37), Yanglingquan (GB34), and Chengshan (BL57) with point-pressing method, plucking method, and kneading method. The stimulating force was 4N, and the stimulating frequency was 60 times per minute; each method and each point were used for 1 minute, totaling 9 minutes (1 min/acupoint/method × 3 methods × 3 acupoints). Treatment was administered for 21 days, followed by a 1-day rest after the 10th treatment, for a total of 20 times of intervention. The sciatic function index (SFI) was used to evaluate the fine movements of the hind limbs of rats in each group. The ultrastructural changes at the point of nerve injury were observed by transmission electron microscopy, and the gene changes at the point of nerve injury were detected using RNA-sequencing (RNA-seq) technology. Results. Compared with the baseline, the SFI of the SNI group and the Tuina group decreased significantly at the 0th intervention (7 days after molding); compared with the SNI group, the SFI of the Tuina group increased at the 10th intervention (P<0.05) and increased significantly at the 15th and 20th intervention (P<0.01). Compared with the Sham group, the myelin sheath integrity of the sciatic nerve in the SNI group was destroyed and the myelin sheath collapsed seriously, even forming myelin sheath ball, accompanied with severe axonal atrophy and mitochondrial degeneration. The tuina intervention could significantly improve the ultrastructure of the nerve injury point, and the nerve fiber myelin sheath in the Tuina group remained intact, without obvious axonal swelling or atrophy. Atrophic thread granules could be seen in the axon, but there were no vacuolated mitochondria. RNA-seq results showed that there were differences at 221 genes at the point of nerve injury between the Tuina group and the SNI group and the differentially expressed genes (DEGs) are enriched in the biological processes related to the regulation of myocyte. Regulations include the regulation of striated muscle cell differentiation, myoblast differentiation, and myotube differentiation. Conclusion. Tuina can improve the fine motor recovery and protect the myelin integrity in rats with peripheral nerve injury, and this is achieved by changing the gene sequence at the injured point.

scholarly journals Peripheral axotomy-induced changes of motor function and histological structure of spinal anterior horn

2019 ◽  
Vol 29 (1) ◽  
Author(s):  
Amir Raoofi ◽  
Mohammad Amin Abdollahifar ◽  
Abbas Aliaghaei ◽  
Abbas Piryaei ◽  
Fatemeh Hejazi ◽  
...  
Keyword(s):  
Sciatic Nerve ◽  
Peripheral Nerve ◽  
Motor Function ◽  
Motor Neurons ◽  
Anterior Horn ◽  
Control Group ◽  
Histological Structure ◽  
Adult Rats ◽  
The Right ◽  
Experimental Group

The aim of this study was to evaluate changes of both peripheral motor function and histology of spinal anterior horn in adult rats after unilateral sciatectomy. Ten adult healthy rats served as control group, while in the ten rat experimental group the right sciatic nerve was severed. We followed-up nerve motor function using a sciatic function index and electromyography activity of the gastrocnemious muscle. The rats of the experimental group presented the expected gross locomotor deficit and leg muscle atrophy. At 12 weeks post sciatectomy, L4 and L5 spinal cord segments were removed from the twenty rats and were analysed by istological stereological methods. In the axotomized animals volume of the anterior horn and its content of motor neurons decreased, while the content of astrocytes increased (p < 0.05). Thus, in adult rats, beside the obvious peripheral nerve disfuction, the sciatic nerve axotomy have severe consequences on the soma of the injured motor neurons in the spinal anterior horn. All these quantitative analyses may be usefull to quantify changes occurring in adult animals after axotomy and eventual management to modify the final outcomes in peripheral nerve disorders.

scholarly journals 4-AP-3-MeOH Promotes Structural and Functional Spontaneous Recovery in the Acute Sciatic Nerve Stretch Injury

Dose-Response ◽  
2020 ◽  
Vol 18 (1) ◽  
pp. 155932581989925
Author(s):  
Yan Chen ◽  
Weidong Wang ◽  
Zhimin Zhao ◽  
Dong Ren ◽  
Danmou Xin
Keyword(s):  
Sciatic Nerve ◽  
Peripheral Nerve ◽  
Nerve Injury ◽  
Motor Function ◽  
Peripheral Nerve Injury ◽  
Spontaneous Recovery ◽  
Sciatic Nerve Injury ◽  
Stretch Injury ◽  
Injured Nerve ◽  
Injury Model

Background: 4-AP-3-MeOH, a derivative of 4-aminopyridine, was developed and demonstrated to prevent nerve pulse diffusion due to myelin damage and significantly enhance axonal conduction following nerve injury. Currently, repurposing the existing drug such as 4-AP-3-MeOH to restore motor function is a promising and potential therapy of peripheral nerve injury. However, to evaluate drug effect on sciatic nerve injury is full of challenge. Methods: Sciatic functional index was used to determine and measure the walking track in the stretch injury model. Nerve conductivity was performed by electrical stimulation of a nerve and recording the compound muscle action potential. Myelin thickness and regeneration was imaged and measured with transmission electron microscopy (TEM). Results: In this study, we developed a sciatic nerve injury model to minimize the spontaneous recovery mechanism and found that 4-AP-3-MeOH not only improved walking ability of the animals but also reduced the sensitivity to thermal stimulus. More interesting, 4-AP-3-MeOH enhanced and recovered electric conductivity of injured nerve; our TEM results indicated that the axon sheath thickness was increased and myelin was regenerated, which was an important evidence to support the recovery of injured nerve conductivity with 4-AP-3-MeOH treatment. Conclusions: In summary, our studies suggest that 4-AP-3-MeOH is a viable and promising approach to the therapy of peripheral nerve injury and in support of repurposing the existing drug to restore motor function.

Changes in Crossed Spinal Reflexes After Peripheral Nerve Injury and Repair

2002 ◽  
Vol 87 (4) ◽  
pp. 1763-1771 ◽  
Author(s):  
Antoni Valero-Cabré ◽  
Xavier Navarro
Keyword(s):  
Sciatic Nerve ◽  
Action Potential ◽  
Peripheral Nerve ◽  
Nerve Injury ◽  
Peripheral Nerve Injury ◽  
Tibialis Anterior ◽  
Tibial Nerve ◽  
Spinal Reflexes ◽  
Injury And Repair

We investigated the changes induced in crossed extensor reflex responses after peripheral nerve injury and repair in the rat. Adults rats were submitted to non repaired sciatic nerve crush (CRH, n = 9), section repaired by either aligned epineurial suture (CS, n = 11) or silicone tube (SIL4, n = 13), and 8 mm resection repaired by tubulization (SIL8, n = 12). To assess reinnervation, the sciatic nerve was stimulated proximal to the injury site, and the evoked compound muscle action potential (M and H waves) from tibialis anterior and plantar muscles and nerve action potential (CNAP) from the tibial nerve and the 4th digital nerve were recorded at monthly intervals for 3 mo postoperation. Nociceptive reinnervation to the hindpaw was also assessed by plantar algesimetry. Crossed extensor reflexes were evoked by stimulation of the tibial nerve at the ankle and recorded from the contralateral tibialis anterior muscle. Reinnervation of the hindpaw increased progressively with time during the 3 mo after lesion. The degree of muscle and sensory target reinnervation was dependent on the severity of the injury and the nerve gap created. The crossed extensor reflex consisted of three bursts of activity (C1, C2, and C3) of gradually longer latency, lower amplitude, and higher threshold in control rats. During follow-up after sciatic nerve injury, all animals in the operated groups showed recovery of components C1 and C2 and of the reflex H wave, whereas component C3 was detected in a significantly lower proportion of animals in groups with tube repair. The maximal amplitude of components C1 and C2 recovered to values higher than preoperative values, reaching final levels between 150 and 245% at the end of the follow-up in groups CRH, CS, and SIL4. When reflex amplitude was normalized by the CNAP amplitude of the regenerated tibial nerve, components C1 (300–400%) and C2 (150–350%) showed highly increased responses, while C3 was similar to baseline levels. In conclusion, reflexes mediated by myelinated sensory afferents showed, after nerve injuries, a higher degree of facilitation than those mediated by unmyelinated fibers. These changes tended to decline toward baseline values with progressive reinnervation but still remained significant 3 mo after injury.

scholarly journals SUR1, newly expressed in astrocytes, mediates neuropathic pain in a mouse model of peripheral nerve injury

2021 ◽  
Vol 17 ◽  
pp. 174480692110066
Author(s):  
Orest Tsymbalyuk ◽  
Volodymyr Gerzanich ◽  
Aaida Mumtaz ◽  
Sanketh Andhavarapu ◽  
Svetlana Ivanova ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Neuropathic Pain ◽  
Sciatic Nerve ◽  
Peripheral Nerve ◽  
Dorsal Horn ◽  
Nerve Injury ◽  
Peripheral Nerve Injury ◽  
Thermal Sensitivity ◽  
Gradual Improvement ◽  
Pain Behaviors

Background Neuropathic pain following peripheral nerve injury (PNI) is linked to neuroinflammation in the spinal cord marked by astrocyte activation and upregulation of interleukin 6 (IL -6 ), chemokine (C-C motif) ligand 2 (CCL2) and chemokine (C-X-C motif) ligand 1 (CXCL1), with inhibition of each individually being beneficial in pain models. Methods Wild type (WT) mice and mice with global or pGfap-cre- or pGFAP-cre/ERT2-driven Abcc8/SUR1 deletion or global Trpm4 deletion underwent unilateral sciatic nerve cuffing. WT mice received prophylactic (starting on post-operative day [pod]-0) or therapeutic (starting on pod-21) administration of the SUR1 antagonist, glibenclamide (10 µg IP) daily. We measured mechanical and thermal sensitivity using von Frey filaments and an automated Hargreaves method. Spinal cord tissues were evaluated for SUR1-TRPM4, IL-6, CCL2 and CXCL1. Results Sciatic nerve cuffing in WT mice resulted in pain behaviors (mechanical allodynia, thermal hyperalgesia) and newly upregulated SUR1-TRPM4 in dorsal horn astrocytes. Global and pGfap-cre-driven Abcc8 deletion and global Trpm4 deletion prevented development of pain behaviors. In mice with Abcc8 deletion regulated by pGFAP-cre/ERT2, after pain behaviors were established, delayed silencing of Abcc8 by tamoxifen resulted in gradual improvement over the next 14 days. After PNI, leakage of the blood-spinal barrier allowed entry of glibenclamide into the affected dorsal horn. Daily repeated administration of glibenclamide, both prophylactically and after allodynia was established, prevented or reduced allodynia. The salutary effects of glibenclamide on pain behaviors correlated with reduced expression of IL-6, CCL2 and CXCL1 by dorsal horn astrocytes. Conclusion SUR1-TRPM4 may represent a novel non-addicting target for neuropathic pain.

Transplantation of Schwann cells in a collagen tube for the repair of large, segmental peripheral nerve defects in rats

2013 ◽  
Vol 119 (3) ◽  
pp. 720-732 ◽  
Author(s):  
Yerko A. Berrocal ◽  
Vania W. Almeida ◽  
Ranjan Gupta ◽  
Allan D. Levi
Keyword(s):  
Sciatic Nerve ◽  
Peripheral Nerve ◽  
Schwann Cells ◽  
Nerve Injury ◽  
Peripheral Nerve Injury ◽  
Fluorescent Protein ◽  
Control Groups ◽  
Myelinated Axons ◽  
Segmental Nerve ◽  
Green Fluorescent

Object Segmental nerve defects pose a daunting clinical challenge, as peripheral nerve injury studies have established that there is a critical nerve gap length for which the distance cannot be successfully bridged with current techniques. Construction of a neural prosthesis filled with Schwann cells (SCs) could provide an alternative treatment to successfully repair these long segmental gaps in the peripheral nervous system. The object of this study was to evaluate the ability of autologous SCs to increase the length at which segmental nerve defects can be bridged using a collagen tube. Methods The authors studied the use of absorbable collagen conduits in combination with autologous SCs (200,000 cells/μl) to promote axonal growth across a critical size defect (13 mm) in the sciatic nerve of male Fischer rats. Control groups were treated with serum only–filled conduits of reversed sciatic nerve autografts. Animals were assessed for survival of the transplanted SCs as well as the quantity of myelinated axons in the proximal, middle, and distal portions of the channel. Results Schwann cell survival was confirmed at 4 and 16 weeks postsurgery by the presence of prelabeled green fluorescent protein–positive SCs within the regenerated cable. The addition of SCs to the nerve guide significantly enhanced the regeneration of myelinated axons from the nerve stump into the proximal (p < 0.001) and middle points (p < 0.01) of the tube at 4 weeks. The regeneration of myelinated axons at 16 weeks was significantly enhanced throughout the entire length of the nerve guide (p < 0.001) as compared with their number in a serum–only filled tube and was similar in number compared with the reversed autograft. Autotomy scores were significantly lower in the animals whose sciatic nerve was repaired with a collagen conduit either without (p < 0.01) or with SCs (p < 0.001) when compared with a reversed autograft. Conclusions The technique of adding SCs to a guidance channel significantly enhanced the gap distance that can be repaired after peripheral nerve injury with long segmental defects and holds promise in humans. Most importantly, this study represents some of the first essential steps in bringing autologous SC-based therapies to the domain of peripheral nerve injuries with long segmental defects.

scholarly journals Histopathological analysis of gangliosides use in peripheral nerve regeneration after axonotmesis in rats

2008 ◽  
Vol 23 (4) ◽  
pp. 364-371 ◽  
Author(s):  
Camila Maria Beder Ribeiro ◽  
Belmiro Cavalcanti do Egito Vasconcelos ◽  
Joaquim Celestino da Silva Neto ◽  
Valdemiro Amaro da Silva Júnior ◽  
Nancy Gurgel Figueiredo
Keyword(s):  
Sciatic Nerve ◽  
Peripheral Nerve ◽  
Nerve Regeneration ◽  
Schwann Cells ◽  
Peripheral Nerve Regeneration ◽  
Cell Activity ◽  
Control Group ◽  
Histopathological Analysis ◽  
Male Wistar Rats ◽  
The Right

PURPOSE: To analyze the action of gangliosides in peripheral nerve regeneration in the sciatic nerve of the rat. METHODS: The sample was composed of 96 male Wistar rats. The animals were anaesthetized and, after identification of the anaesthesic plane, an incision was made in the posterior region of the thigh, followed by skin and muscle divulsion. The right sciatic nerve was isolated and compressed for 2 minutes. Continuous suture of the skin was performed. The animals were randomly divided into two groups: the experimental group (EG), which received subcutaneous injection of gangliosides, and the control group (CG), which received saline solution (0.9%) to mimic the effects of drug administration. RESULTS: No differences were observed between the experimental and control groups evaluated on the eighth day of observation. At 15 and 30 days the EG showed an decrease in Schwann cell activity and an apparent improvement in fibre organization; at 60 days, there was a slight presence of Schwann cells in the endoneural space and the fibres were organized, indicating nerve regeneration. At 15 and 30 days, the level of cell reaction in the CG had diminished, but there were many cells with cytoplasm in activity and in mitosis; at 60 days, hyperplastic Schwann cells and mitotic activity were again observed, as well as nerve regeneration, but to a lesser extent than in the EG. CONCLUSION: The administration of exogenous gangliosides seems to improve nerve regeneration.

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