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 Strychnos nux-vomica L. seed preparation promotes functional recovery and attenuates oxidative stress in a mouse model of sciatic nerve crush injury

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Aroona Razzaq ◽  
Ghulam Hussain ◽  
Azhar Rasul ◽  
Jiaqi Xu ◽  
Qiqi Zhang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Sciatic Nerve ◽  
Mouse Model ◽  
Muscle Mass ◽  
Functional Recovery ◽  
Sensory Function ◽  
Sciatic Nerve Crush ◽  
Nerve Lesion ◽  
Active Constituent ◽  
Platelet Counts

Abstract Background Peripheral nerve injury is a debilitating condition that may lead to partial or complete motor, sensory and autonomic function loss and lacks effective therapy until date. Therefore, it is quite imperative to explore impending remedies for rapid and accurate functional retrieval following such conditions. Natural product-based intervention can prove effective to facilitate the process of functions regain. Methods Here, we investigated the effect of processed Strychnos nux-vomica seeds at a dose of 250 mg/kg body weight in a mouse model of induced Sciatic nerve lesion in promoting the recovery of the functions. A compression injury was induced in the Sciatic nerve of the right leg in the mice. Sensory function recovery was evaluated by hot-plate and formalin tests, whereas the motor function retrieval was assessed by measuring muscle grip strength, sciatic functional index, and muscle mass restoration. Oxidative stress and blood cell count were measured by biochemistry and haematological analyses. Results This study indicates that Strychnos nux-vomica seeds enhance the rate of recovery of both sensory and motor functions. It helps restore the muscle mass, attenuates total oxidant status and enhances the total anti-oxidant capacity of the biological system. Moreover, the treated animals manifested an enhanced glucose tolerance aptitude and augmented granulocyte and platelet counts. Improved oxidant control, enhanced glucose sensitivity and amended granulocyte and platelet counts are likely to contribute to the advantageous effects of Strychnos nux-vomica, and warrant further in-depth studies for deciphering possible mechanisms and identification of active constituent(s) responsible for these effects. Conclusion Strychnos nux-vomica seed offers functional recovery promoting effects following a mechanical injury to the Sciatic nerve and the possible reasons behind this effect can be reduced oxidative stress and improved glycaemic control. Further and detailed investigations can unravel this mystery.

scholarly journals Ultramicronized Palmitoylethanolamide and Paracetamol, a New Association to Relieve Hyperalgesia and Pain in a Sciatic Nerve Injury Model in Rat

2020 ◽  
Vol 21 (10) ◽  
pp. 3509 ◽  
Author(s):  
Alessio Filippo Peritore ◽  
Rosalba Siracusa ◽  
Roberta Fusco ◽  
Enrico Gugliandolo ◽  
Ramona D’Amico ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Sciatic Nerve ◽  
Nerve Injury ◽  
Cell Activation ◽  
Sciatic Nerve Injury ◽  
Sensory Function ◽  
Mast Cell Activation ◽  
Neuroprotective Effects ◽  
New Association ◽  
Ultramicronized Palmitoylethanolamide

Inflammation is known to be an essential trigger of the pathological changes that have a critical impact on nerve repair and regeneration; moreover, damage to peripheral nerves can cause a loss of sensory function and produces persistent neuropathic pain. To date, various potential approaches for neuropathic pain have focused on controlling neuroinflammation. The aim of this study was to investigate the neuroprotective effects of a new association of ultramicronized Palmitoylethanolamide (PEAum), an Autacoid Local Injury Antagonist Amide (ALIAmide) with analgesic and anti-inflammatory properties, with Paracetamol, a common analgesic, in a rat model of sciatic nerve injury (SNI). The association of PEAum–Paracetamol, in a low dose (5 mg/kg + 30 mg/kg), was given by oral gavage daily for 14 days after SNI. PEAum–Paracetamol association was able to reduce hyperalgesia, mast cell activation, c-Fos and nerve growth factor (NGF) expression, neural histological damage, cytokine release, and apoptosis. Furthermore, the analgesic action of PEAum–Paracetamol could act in a synergistic manner through the inhibition of the NF-κB pathway, which leads to a decrease of cyclooxygenase 2-dependent prostaglandin E2 (COX-2/PGE2) release. In conclusion, we demonstrated that PEAum associated with Paracetamol was able to relieve pain and neuroinflammation after SNI in a synergistic manner, and this therapeutic approach could be relevant to decrease the demand of analgesic drugs.

Transcriptomic Analysis Reveals PTBP1 as a Key Molecular Signature of Sciatic Nerve Injury Recovery

2021 ◽  
Author(s):  
Zijia Chai ◽  
Jinjin Fu ◽  
Zhe Yang ◽  
Yi E. Sun
Keyword(s):  
Sciatic Nerve ◽  
Nerve Injury ◽  
Early Stage ◽  
Sciatic Nerve Injury ◽  
Sensory Function ◽  
Molecular Signature ◽  
Control Group ◽  
P Value ◽  
Immunofluorescence Test ◽  
Hub Genes

Abstract Background: Peripheral nerves control motor, sensory, and autonomic functions, so injury can seriously affect a patient's quality of life. There have been studies that have shown that the repair factors are different at different ages, and we have identified a repair hub gene that plays a key role throughout the entire age group. Methods: From Gene Expression Omnibus database GSE4090, mice of 2 and 24 months of age after sciatic nerve injury were selected from mice transcriptome data of differentially expressed genes in common, and the hub genes were then determined using protein-protein network and MCODE analysis, DAVID biological process, molecular function, and cell component analysis, and the miRWalk analysis of hub genes was performed to verify the key molecule. In mice aged eight weeks of sciatic 2 nerve clamps damage building, on days 0, 1, 4, and 7, sciatic nerve motor and sensory function were evaluated, and sciatic nerve immunofluorescence test was performed to verify PTBP1 expression. The continuous data were expressed as the mean ±SD. An independent t-test was used to compare two groups. A p-value of less than 0.05 was considered statistically significant. Results: Bioinformatics analysis showed that PTBP1 is one of the key molecules in mouse sciatic nerve repair after injury. The immunofluorescence test verified that the number of positive cells reached a maximum value of 30.6 ±6.4/ROI on day 7 after injury and a minimum value of 17.4 ±7.0/ROI in the control group (p<0.001). However, the percentage of PTBP1 positive cells reached a peak of 90.8 ±16.9% at the early stage of injury, i.e., the first day, and then dropped to a minimum of 75.7 ±8.9% on the seventh day in the animal experiment as the repair time gradually increased (p<0.05). Conclusions: PTBP1 plays a key role in the repair of sciatic nerve injury, providing a new strategy for clinical treatment of patients of all ages.

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 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.

Micro- and Astroglia Activity in the Spinal Cord Ventrolateral Nucleus Sciatic Nerve Injury in Rats

2020 ◽  
Vol 14 (4) ◽  
pp. 263-269
Author(s):  
A. A. Starinets ◽  
E. L. Egorova ◽  
A. A. Tyrtyshnaia ◽  
I. V. Dyuisen ◽  
A. N. Baryshev ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Sciatic Nerve ◽  
Nerve Injury ◽  
Sciatic Nerve Injury ◽  
Ventrolateral Nucleus

scholarly journals 3D-printed nerve guidance conduits multi-functionalized with canine multipotent mesenchymal stromal cells promote neuroregeneration after sciatic nerve injury in rats

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Diego Noé Rodríguez-Sánchez ◽  
Giovana Boff Araujo Pinto ◽  
Luciana Politti Cartarozzi ◽  
Alexandre Leite Rodrigues de Oliveira ◽  
Ana Livia Carvalho Bovolato ◽  
...  
Keyword(s):  
Growth Factor ◽  
Sciatic Nerve ◽  
Nerve Injury ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Multipotent Mesenchymal Stromal Cells ◽  
Sciatic Nerve Injury ◽  
Motor Deficits ◽  
3D Printed

Abstract Background Nerve injuries are debilitating, leading to long-term motor deficits. Remyelination and axonal growth are supported and enhanced by growth factor and cytokines. Combination of nerve guidance conduits (NGCs) with adipose-tissue-derived multipotent mesenchymal stromal cells (AdMSCs) has been performing promising strategy for nerve regeneration. Methods 3D-printed polycaprolactone (PCL)-NGCs were fabricated. Wistar rats subjected to critical sciatic nerve damage (12-mm gap) were divided into sham, autograft, PCL (empty NGC), and PCL + MSCs (NGC multi-functionalized with 106 canine AdMSCs embedded in heterologous fibrin biopolymer) groups. In vitro, the cells were characterized and directly stimulated with interferon-gamma to evaluate their neuroregeneration potential. In vivo, the sciatic and tibial functional indices were evaluated for 12 weeks. Gait analysis and nerve conduction velocity were analyzed after 8 and 12 weeks. Morphometric analysis was performed after 8 and 12 weeks following lesion development. Real-time PCR was performed to evaluate the neurotrophic factors BDNF, GDNF, and HGF, and the cytokine and IL-10. Immunohistochemical analysis for the p75NTR neurotrophic receptor, S100, and neurofilament was performed with the sciatic nerve. Results The inflammatory environment in vitro have increased the expression of neurotrophins BDNF, GDNF, HGF, and IL-10 in canine AdMSCs. Nerve guidance conduits multi-functionalized with canine AdMSCs embedded in HFB improved functional motor and electrophysiological recovery compared with PCL group after 12 weeks. However, the results were not significantly different than those obtained using autografts. These findings were associated with a shift in the regeneration process towards the formation of myelinated fibers. Increased immunostaining of BDNF, GDNF, and growth factor receptor p75NTR was associated with the upregulation of BDNF, GDNF, and HGF in the spinal cord of the PCL + MSCs group. A trend demonstrating higher reactivity of Schwann cells and axonal branching in the sciatic nerve was observed, and canine AdMSCs were engrafted at 30 days following repair. Conclusions 3D-printed NGCs multi-functionalized with canine AdMSCs embedded in heterologous fibrin biopolymer as cell scaffold exerted neuroregenerative effects. Our multimodal approach supports the trophic microenvironment, resulting in a pro-regenerative state after critical sciatic nerve injury in rats.

Arginase-1 deficiency in neural cells does not contribute to neurodevelopment or functional outcomes after sciatic nerve injury

2021 ◽  
Vol 145 ◽  
pp. 104984
Author(s):  
Christopher R. Richmond ◽  
Laurel L. Ballantyne ◽  
A. Elizabeth de Guzman ◽  
Brian J. Nieman ◽  
Colin D. Funk ◽  
...  
Keyword(s):  
Sciatic Nerve ◽  
Nerve Injury ◽  
Functional Outcomes ◽  
Sciatic Nerve Injury ◽  
Neural Cells ◽  
Arginase 1
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