Nerve Crush Injury In Rats Research Articles

Activation of PAR1 contributes to ferroptosis of Schwann cells and inhibits regeneration of myelin sheath after sciatic nerve crush injury in rats via Hippo-YAP/ACSL4 pathway.

Peripheral nerve injury (PNI) is characterized by high incidence and sequela rate. Recently, there was increasing evidence that has shown ferroptosis may impede functional recovery. Our objective is to explore the novel mechanism that regulates ferroptosis after PNI. LC-MS/MS proteomics was used to explore the possible differential signals, while PCR array was performed to investigate the differential factors. Besides, we also tried to activate or inhibit the key factors and then observe the level of ferroptosis. Regeneration of myelin sheath was finally examined in vivo via transmission electron microscopy. Proteomics analysis suggested coagulation signal was activated after sciatic nerve crush injury, in which high expression of F2 (encoding thrombin) and F2r (encoding PAR1) were observed. Both thrombin and PAR1-targeted activator TRAP6 can induce ferroptosis in RSC96 cells, which can be rescued by Vorapaxar (PAR1 targeted inhibitor) in vitro. Further PCR array revealed that activation of PAR1 induced ferroptosis in RSC96 cells by increasing expression of YAP and ACSL4. Immunofluorescence of sciatic nerve confirmed that the expression of YAP and ACSL4 were simultaneously reduced after PAR1 inhibition, which may contribute to myelin regeneration after injury in SD rats. Inhibition of PAR1 can relieve ferroptosis after sciatic nerve crush injury in SD rats through Hippo-YAP/ACSL4 pathway, thereby regulating myelin regeneration after injury. In summary, PAR1/Hippo-YAP/ACSL4 pathway may be a promising therapeutic target for promoting functional recovery post-sciatic crush injury.

Oxidized sodium alginate hydrogel-mouse nerve growth factor sustained release system promotes repair of peripheral nerve injury

In recent years, mouse nerve growth factor (mNGF) has emerged as an important biological regulator to repair peripheral nerve injury, but its systemic application is restricted by low efficiency and large dosage requirement. These limitations prompted us to search for biomaterials that can be locally loaded. Oxidized sodium alginate hydrogel (OSA) exhibits good biocompatibility and physicochemical properties, and can be loaded with drugs to construct a sustained-release system that can act locally on nerve injury. Here, we constructed a sustained-release system of OSA-mouse nerve growth factor (mNGF), and investigated the loading and release of the drug through Fourier transform infrared spectroscopy and drug release curves. In vitro and in vivo experiments showed that OSA-mNGF significantly promoted the biological activities of RSC-96 cells and facilitated the recovery from sciatic nerve crush injury in rats. This observation may be attributed to the additive effect of OSA on promoting Schwann cell biological activities or its synergistic effect of cross-activating phosphoinositide 3-kinase (PI3K) through extracellular signal regulated kinase (ERK) signaling. Although the specific mechanism of OSA action needs to be explored in the future, the current results provide a valuable preliminary research basis for the clinical application of the OSA-mNGF sustained-release system for nerve repair.

HucMSCs Delay Muscle Atrophy After Peripheral Nerve Injury Through Exosomes by Repressing Muscle-Specific Ubiquitin Ligases.

Cell therapy based on mesenchymal stem cells (MSCs) alleviate muscle atrophy caused by diabetes and aging; however, the impact of human umbilical cord mesenchymal stem cells on muscle atrophy following nerve injury and the underlying mechanisms remain unclear. In this study, we evaluated the therapeutic efficacy of human umbilical cord MSCs (hucMSCs) and hucMSC-derived exosomes (hucMSC-EXOs) for muscle atrophy following nerve injury and identified the underlying molecular mechanisms. Sciatic nerve crush injury in rats and the induction of myotubes in L6 cells were used to determine the ameliorating effect of hucMSCs and hucMSC-EXOs on muscle atrophy. Q-PCR and Western blot analyses were used to measure the expression of muscle-specific ubiquitin ligases Fbxo32 (Atrogin1, MAFbx) and Trim63 (MuRF-1). Dual-luciferase reporter gene experiments were conducted to validate the direct binding of miRNAs to their target genes. Local injection of hucMSCs and hucMSC-EXOs mitigated atrophy in the rat gastrocnemius muscle following sciatic nerve crush injury. In vitro, hucMSC-EXOs alleviated atrophy in L6 myotubes. Mechanistic analysis indicated the upregulation of miR-23b-3p levels in L6 myotubes following hucMSC-EXOs treatment. MiR-23b-3p significantly inhibited the expression of its target genes, Fbxo32 and Trim63, and suppressed myotube atrophy. Notably, an miR-23b-3p inhibitor reversed the inhibitory effect of miR-23b-3p on myotube atrophy in vitro. These results suggest that hucMSCs and their exosomes alleviate muscle atrophy following nerve injury. MiR-23b-3p in exosomes secreted by hucMSCs contributes to this mechanism by inhibiting the muscle-specific ubiquitination ligases Fbxo32 and Trim63.

Morphofunctional regeneration by mesenchymal stem cell and IGF-1 inoculation in a model of facial nerve crush injury in rats.

To analyze the morphofunctional regeneration process of facial nerve injury in the presence of insulin-like growth factor-1 and mesenchymal stem cells. Fourteen Wistar rats suffered unilateral facial nerve crushing and were randomly divided into two groups. All received insulin-like growth factor-1 inoculation, but only half of the animals received an additional inoculation of mesenchymal stem cells. The animals were followed for 90 days and facial nerve regeneration was analyzed via spontaneous facial motor function tests and immunohistochemistry in the nerve motor nucleus. The group that received the growth factor and stem cells showed a statistically superior mean in vibrissae movements (p < 0.01), touch reflex (p = 0.05) and eye closure (p < 0.01), in addition to better immunohistochemistry reactivity. There was a statistically significant difference in the mean number of cells in the facial nerve nucleus between the experimental groups (p = 0.025), with the group that received the growth factor and stem cells showing the highest mean. The association between growth factor and stem cells potentiates the morphofunctional regeneration of the facial nerve, occurring faster and more effectively. 4, degree of recommendation C.

The effect of Alpha-Lipoic Acid on nerve tissue healing after sciatic nerve crush injury in rats

Background: Crush injury damages the nerve, affects its function and causes oxidative stress. Alpha-lipoic acid (ALA) is an antioxidant agent with protective effects on the nerve tissue. In this study, we aimed to investigate the effects of ALA in the treatment of crush sciatic nerve injury in rats. Materials and Methods: Forty rats were divided into five groups. Walking Track Analysis (WTA) was performed in all groups before sacrificing the sciatic nerve. In group I (sham group), the sciatic nerve was exposed but not crushed, whereas in group II (early control group, 24th hour), group III (late control group, 7th day), group IV (early experimental group, 24th hour), and group V (late control group, 7th day), the sciatic nerve was exposed and clipped with an aneurysm clip for 300 seconds. One hour after the crush injury, subjects in groups II and III were given saline (2.5 ml, intraperitoneally), while ALA (100 mg/kg, intraperitoneally) was administered in Groups IV and V. WTA was performed in Groups I, II, and IV at the 24th hour after clipping and was performed in Groups III and V at 7th day after clipping. In all groups, the Sciatic Functional Index (SFI) was calculated after WTA. Following the completion of WTA, sciatic nerve tissue samples were obtained for the measurement of malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT) enzyme values. Results: The SFI scores in groups II, III, IV, and V were significantly lower than that of sham group (p˂0.05), while no significant difference was found between groups II and IV and between groups III and V (p&gt;0.05). The CAT values of groups II and IV, the GSH-Px value and MDA value of group IV, and the SOD values of groups II and IV were found to be significantly higher than those of sham group (p&lt;0.05). However, no significant difference was found among groups I, III, and V with regard to CAT, GSH-Px, MDA and SOD values (p&gt;0.05). Conclusion: The results indicated that a single dose of ALA (100 mg/kg) administered intraperitoneally one hour after the sciatic nerve crush injury had no therapeutic efficacy at 24 hours and 7 days after the administration. Further experimental studies are needed to evaluate the effectiveness of ALA applied in several doses rather than a single dose in crush peripheral nerve injury models.

Evaluation of the therapeutic effects of calcium dobesilate in sciatic nerve crush injury in rats

IntroductionProinflammatory cytokines released from nerve endings and surrounding injured tissue after nerve damage can prolong the inflammation process, delay nerve healing or result in poor quality nerve healing. In this case, due to the loss of function in the muscles innervated by the damaged nerve, the patient may have neurological and functional difficulties which may reduce the patient's quality of life and create an economic burden. Although the attempts of many pharmacological agents to heal crush injury of peripheral nerves have been recorded in literature, a drug that can provide adequate recovery of the crushed nerve and can be applied in daily life has not been defined as yet. This study aimed to assess the effects of calcium dobesilate on sciatic nerve crush injury in a rat model. MethodsA total of 26 male Wistar albino rats were separated into four groups as follows: CONTROL group (healthy subjects, n=6); SHAM group (crush injury was created, n=6); MP group (after created crush injury, methylprednisolone was administered, n=7); and CAD group (after created crush injury, calcium dobesilate was administered, n=7). A crush injury was created, then the electrophysiological findings and sciatic nerve functional index (SFI) were recorded before euthanasia. After the euthanasia of all the rats, samples of the crushed nerve and gastrocnemius muscle were evaluated histopathologically, immunohistochemically, and biochemically. ResultsBoth pharmacological agents were histopathologically effective in axon regeneration and repair. Calcium dobesilate did not preserve total muscle mass but was seen to prevent atrophy microscopically. Immunohistochemistry and biochemistry results showed that calcium dobesilate and methylprednisolone had anti-inflammatory, anti-oxidant, anti-apoptotic, and anti-autophagic activity in the crushed sciatic nerve. Neither calcium dobesilate nor methylprednisolone improved the nerve conductance level. SFI values obtained on day 30 from the CAD group were numerically closer to the values of the healthy animals but not at a statistically significant level. ConclusionThe study results demonstrated that calcium dobesilate could suppress inflammatory processes and provide histopathological and functional improvements in the injured nerve in rats. Therefore, further clinical studies are recommended to investigate in detail the therapeutic effects of calcium dobesilate on peripheral nerve crush injury.

Effects of Cells Self-aggregation in the Treatment of Neurogenic Erectile Dysfunction With Traditional Single Cell Suspension of Adipose-derived Stem Cells

ObjectiveTo clarify the effects of cellular self-aggregation of adipose-derived stem cells (ADSCs) on erectile function (EF). MethodsA model of neurogenic erectile dysfunction was performed using bilateral cavernous nerve crush injury in rats. ADSCs suspensions (1 × 106/0.2 ml), were administered via intracavernous injection (ICI) after being allowed to shelve for 0 minute (ICI 0) or 60 minutes (ICI 60) in vitro, as well as cell aggregates isolated from ICI 60 (ICI A). The caudal vein injection group (CVI 60) was used to evaluate whether cell self-aggregation was beneficial to EF when introduced into the peripheral circulation. One day after the transplantation, the distribution of cells was observed. EF and histopathological changes were evaluated after 4 weeks. ResultsApproximately 85% of ADSCs self-aggregated into cell clusters at 60 minutes. The ICI 60 had more significant improvements in EF and more visualized ADSCs retained in the corpus cavernosum (CC) than ICI 0 and CVI 60 (P <.05), but no significant difference between ICI 60 and ICI A. In the CVI 60 group, the cell clusters formed by self-aggregation could hardly reach the CC and were mostly found in lung tissue. Immunofluorescence staining showed increased the content of expressing biomarkers of smooth muscle, nerve within the CC tissue in the ICI groups when compared to the CVI group. ConclusionADSCs self-aggregation before ICI may be an influential factor in the treatment of neurogenic erectile dysfunction. Its potential mechanism may be through improving cell retention in the CC.

Diterpene Ginkgolides Meglumine Injection inhibits apoptosis induced by optic nerve crush injury via modulating MAPKs signaling pathways in retinal ganglion cells

Ethnopharmacological relevanceDiterpene Ginkgolides Meglumine Injection (DGMI) is made of extracts from Ginkgo biloba L, including Ginkgolides A, B, and K and some other contents, and has been widely used as the treatment of cerebral ischemic stroke in clinic. It can be learned from the “Compendium of Materia Medica” that Ginkgo possesses the effect of “dispersing toxin”. The ancient Chinese phrase “dispersing toxin” is now explained as elimination of inflammation and oxidative state in human body. And it led to the original ideas for today's anti-oxidation studies of Ginkgo in apoptosis induced by optic nerve crush injury. Aim of the studyTo investigate the underlying molecular mechanism of the DGMI in retinal ganglion cells (RGCs) apoptosis. Materials and methodsTUNEL staining was used to observe the anti-apoptotic effects of DGMI on the adult rat optic nerve injury (ONC) model, and flow cytometry and hoechst 33,342 staining were used to observe the anti-apoptotic effects of DGMI on the oxygen glucose deprivation (OGD) induced RGC-5 cells injury model. The regulation of apoptosis and MAPKs pathways were investigated with Immunohistochemistry and Western blotting. ResultsThis study demonstrated that DGMI is able to decrease the conduction time of F-VEP and ameliorate histological features induced by optic nerve crush injury in rats. Immunohistochemistry and TUNEL staining results indicated that DGMI can also inhibit cell apoptosis via modulating MAPKs signaling pathways. In addition, treatment with DGMI markedly improved the morphological structures and decreased the apoptotic index in RGC-5 cells. Mechanistically, DGMI could significantly inhibit cell apoptosis by inhibiting p38, JNK and Erk1/2 activation. ConclusionThe study shows that DGMI and ginkgolides inhibit RGCs apoptosis by impeding the activation of MAPKs signaling pathways in vivo and in vitro. Therefore, the present study provided scientific evidence for the underlying mechanism of DGMI and ginkgolides on optic nerve crush injury.

Neuroprotective Effect of Brimonidine against Facial Nerve Crush Injury in Rats via Suppressing GFAP/PAF Activation and Neuroinflammation

Objective: This study aimed to investigate the potential neuroprotective action of brimonidine against facial nerve crush injury in rats and the possible underlying mechanisms. Methods: Sixty Wistar adult rats were randomly and equally divided into 3 groups: 40 rats underwent unilateral facial nerve crush injury and were administered with either saline (intraperitoneal, n = 20) or brimonidine 1 mg/kg/day (intraperitoneal, n = 20) for 5 consecutive days. Functional and electromyographic recovery was recorded postoperatively. The facial nucleus of 5 mice in each group was analyzed for mRNA expression levels of GFAP, PAF, NT-4, P75^NTR, NF-κB, TNF-α, IL-6, and α₂-ARs by qRT-PCR. Results: Brimonidine promoted the recovery of vibrissae movement, eyelid closure, and electrophysiological function in a rat model of nerve crush injury. Hematoxylin and eosin staining and electron microscopy showed significant recovery of Schwann cells and axons in the brimonidine group. Brimonidine attenuated the crush-induced upregulation in GFAP and PAF mRNA (p < 0.05), as well as enhanced the mRNA levels of NT-4 and P75^NTR (p < 0.05), while decreased the expression of NF-κB, TNF-α and IL-6 (p < 0.05). Conclusions: Brimonidine could promote the recovery of facial nerve crush injury in rats via suppressing of GFAP/PAF activation and neuroinflammation and increasing neurotrophic factors. Brimonidine may be apromising candidate agent for the treatment of facial nerve injury.

Catfish Epidermal Preparation Accelerates Healing of Damaged Nerve in a Sciatic Nerve Crush Injury Rat Model.

Preliminary investigations showed that preparations from Arabian Gulf catfish (Arius bilineatus, Val) epidermal gel secretion (PCEGS) exhibit potent anti-inflammatory and healing properties as shown in our previous clinical trials for the healing of non-healing diabetic foot ulcers, chronic back pain, and some other neurological disorders. Here, we report for the first time a unique preparation containing only proteins and lipids (soluble protein fraction B, SPF-FB), derived from the PCEGS accelerated the healing and recovery of sensory-motor functions of experimental sciatic nerve crush injury in rats with its unique neuroprotective and neuroregenerative properties on the spinal neurons and peripheral nerve fibers. Male rats were randomly assigned to five groups: (I) NAÏVE, (II) SHAM, (III) CRUSH treated with saline, (IV) CRUSH + SPF-FB treated with 3 mg/kg intraperitoneally (IP) and (V) CRUSH + SPF-FB treated with 6 mg/kg subcutaneously (SC) groups. The crush groups III, IV and V underwent sciatic nerve crush injury, followed by treatment daily for 14 days with saline, SPF-FB IP and SPF-FB SC. All animals were tested for the neurobehavioral parameters throughout the 6 weeks of the study. Sciatic nerve and spinal cord tissues were processed for light and electron histological examinations, stereological analysis, immunohistochemical and biochemical examinations at Week 4 and Week 6 post-injury. Administration of SPF-FB IP or SC significantly enhanced the neurobehavioral sensory and motor performance and histomorphological neuroregeneration of the sciatic nerve-injured rats. The stereological evaluation of the axon area, average axon perimeters, and myelin thickness revealed significant histomorphological evidence of neuroregeneration in the FB-treated sciatic nerve crush injured groups compared to controls at 4 and 6 weeks. SPF-FB treatment significantly prevented the increased in NeuN-immunoreactive neurons, increased GFAP immunoreactive astrocytes, and decreased GAP-43. We conclude that SPF-FB treatment lessens neurobehavioral deficits, enhances axonal regeneration following nerve injury. We conclude that SPF-FB treatment lessens neurobehavioral deficits and enhances axonal regeneration following nerve injury, as well as protects spinal neurons and enhances subcellular recovery by increasing astrocytic activity and decreasing GAP-43 expression.

Low-Intensity Pulsed Ultrasound Prompts Both Functional and Histologic Improvements While Upregulating the Brain-Derived Neurotrophic Factor Expression after Sciatic Crush Injury in Rats

The aim of this study was to determine that low-intensity pulsed ultrasound (LIPUS) at an intensity of 140 mW/cm2 promotes functional and histologic improvements in sciatic nerve crush injury in a rat model and to investigate changes over time in relevant growth factors and receptors, exploring the mechanism of LIPUS in the recovery process after injury. Toe angle in the toe-off phase, regenerative axonal length, myelinated nerve fiber density, diameter of myelinated nerve fiber, axon diameter and myelin sheath thickness were significantly higher in the LIPUS group than in the sham group. Gene and protein expression of brain-derived neurotrophic factor (BDNF) was upregulated in the LIPUS group. In conclusion, LIPUS contributed to rapid functional and histologic improvement and upregulated BDNF expression after sciatic nerve crush injury in rats.

Characteristics of cytokines in the sciatic nerve stumps and DRGs after rat sciatic nerve crush injury

BackgroundCytokines are essential cellular modulators of various physiological and pathological activities, including peripheral nerve repair and regeneration. However, the molecular changes of these cellular mediators after peripheral nerve injury are still unclear. This study aimed to identify cytokines critical for the regenerative process of injured peripheral nerves.MethodsThe sequencing data of the injured nerve stumps and the dorsal root ganglia (DRGs) of Sprague-Dawley (SD) rats subjected to sciatic nerve (SN) crush injury were analyzed to determine the expression patterns of genes coding for cytokines. PCR was used to validate the accuracy of the sequencing data.ResultsA total of 46, 52, and 54 upstream cytokines were differentially expressed in the SNs at 1 day, 4 days, and 7 days after nerve injury. A total of 25, 28, and 34 upstream cytokines were differentially expressed in the DRGs at these time points. The expression patterns of some essential upstream cytokines are displayed in a heatmap and were validated by PCR. Bioinformatic analysis of these differentially expressed upstream cytokines after nerve injury demonstrated that inflammatory and immune responses were significantly involved.ConclusionsIn summary, these findings provide an overview of the dynamic changes in cytokines in the SNs and DRGs at different time points after nerve crush injury in rats, elucidate the biological processes of differentially expressed cytokines, especially the important roles in inflammatory and immune responses after peripheral nerve injury, and thus might contribute to the identification of potential treatments for peripheral nerve repair and regeneration.

Regenerative Impact (Capacity) of Cerebrolysin versus N-Acetyl- Cysteine on Facial Nerve injury in Rats

Background: Facial nerve (FN) injury is an important health issue worldwide and the most essential principle for all surgeonsis proper diagnosis and early treatment.Aim of the study: Evaluation of the effect of Cerebrolysin (CBL) versus N-acetyl-cysteine (NAC) on FN regeneration.Materials and Methods: Normal 24 Sprague Dawely adult male rats were selected with a weight range 250 - 300 gm. CrushtypeFN injury was performed on the right side of all rats then, they were randomly divided into three equal groups of eightrats each. In group I, the rats were left without any treatment and considered as a control. Rats of group II received 50 mg/kg/day NAC intraperitoneally for a period of 28 days while rats of group III received 2.5 ml/kg/day CBL intraperitoneallyfor the same period. Postoperatively, eye-blink reflex was used to evaluate the functional recovery after the 2nd and the 4thweeks. All animals were euthanized by overdose of diethyl ether after 28 days and nerve regeneration was evaluated based onhistopathological and immunohistochemical (IHC) examinations. All data collected were analyzed using SPSS version 20.0software. Statistical significance was inferred at a P value ≤ 0.05.Results: Nerve regeneration was obvious in group III with significant improvement of the eye-blink reflex at 2weeks period thatbecame non-significant at 4 weeks. Histological and IHC evaluation revealed high regeneration and minimum inflammation ingroup III when compared with groups I and II.Conclusion: CBL enhances nerve regeneration and rehabilitation better than NAC after facial nerve crush injury in rats.

Satellite cell proliferation and myofiber cross-section area increase after electrical stimulation following sciatic nerve crush injury in rats.

BackgroundElectrical stimulation has been recommended as an effective therapy to prevent muscle atrophy after nerve injury. However, the effect of electrical stimulation on the proliferation of satellite cells in denervated muscles has not yet been fully elucidated. This study was aimed to evaluate the changes in satellite cell proliferation after electrical stimulation in nerve injury and to determine whether these changes are related to the restoration of myofiber cross-section area (CSA).MethodsSciatic nerve crush injury was performed in 48 male Sprague-Dawley rats. In half (24/48) of the rats, the gastrocnemius was electrically stimulated transcutaneously on a daily basis after injury, while the other half were not stimulated. Another group of 24 male Sprague-Dawley rats were used as sham operation controls without injury or stimulation. The rats were euthanized 2, 4, and 6 weeks later. After 5-bromo-2’-deoxyuridine (BrdU) labeling, the gastrocnemia were harvested for the detection of paired box protein 7 (Pax7), BrdU, myofiber CSA, and myonuclei number per fiber. All data were analyzed using two-way analysis of variance and Bonferroni post-hoc test.ResultsThe percentages of Pax7-positive nuclei (10.81 ± 0.56%) and BrdU-positive nuclei (34.29 ± 3.87%) in stimulated muscles were significantly higher compared to those in non-stimulated muscles (2.58 ± 0.33% and 1.30 ± 0.09%, respectively, Bonferroni t = 15.91 and 18.14, P < 0.05). The numbers of myonuclei per fiber (2.19 ± 0.24) and myofiber CSA (1906.86 ± 116.51 μm2) were also increased in the stimulated muscles (Bonferroni t = 3.57 and 2.73, P < 0.05), and both were positively correlated with the Pax7-positive satellite cell content (R2 = 0.52 and 0.60, P < 0.01). There was no significant difference in the ratio of myofiber CSA/myonuclei number per fiber among the three groups.ConclusionsOur results indicate that satellite cell proliferation is promoted by electrical stimulation after nerve injury, which may be correlated with an increase in myonuclei number and myofiber CSA.

Dexmedetomidine Improves Locomotor Function and Alleviates Thermal Hyperalgesia Following Sciatic Nerve Crush Injury in Rats.

PurposeThe effects of dexmedetomidine on locomotor function and thermal hyperalgesia in sciatic nerve crush injury (SNCI) were investigated using rats.MethodsAfter exposing the right sciatic nerve, the sciatic nerve was crushed for 1 minute by a surgical clip. One day after nerve injury, dexmedetomidine (5, 25, and 50 µg/kg) was directly applied to the injured sciatic nerve once a day for 14 days. Walking track analysis was used to assess locomotor function and plantar test was conducted to assess thermal pain sensitivity. Immunohistochemistry was performed to determine the expression of c-Fos in the ventrolateral periaqueductal gray (vlPAG) and paraventricular nucleus (PVN). Western blot was used to evaluate the expression level of nerve growth factor (NGF) and myelin basic protein (MBP) in the sciatic nerve.ResultsSNCI resulted in deterioration of locomotor function and increased thermal pain sensitivity. The level of c-Fos expression in the PVN and vlPAG was increased and the level of NGF and MBP expression in the sciatic nerve was enhanced by SNCI. Dexmedetomidine treatment improved locomotor function and upregulated expression of NGF and MBP in the sciatic nerve of SNCI. Dexmedetomidine treatment alleviated thermal hyperalgesia and downregulated expression of c-Fos in the vlPAG and PVN after SNCI.ConclusionsDexmedetomidine may be used as a potential new treatment drug for recovery of locomotion and control of pain in peripheral nerve injury.

Cinnamaldehyde Enhanced Functional Recovery after Sciatic Nerve Crush Injury in Rats

Peripheral nerve injury is a common clinical issue induced by trauma, tumor, and damage caused by treatment. Such factors create chemical and inflammatory alterations at the injury site, which increase nerve deterioration. Thus, minimizing these modifications can lead to nerve protection after injury. The present study sought to evaluate the possible improvement in nerve regeneration and enhancement of functional outcomes by cinnamaldehyde (Cin) administration following sciatic nerve crush in a rat model. Rats (n = 48) were distributed into 6 groups, including sham, injury, DMSO (vehicle group), and Cin groups (10, 30, and 90 mg/kg/day). Using small hemostatic forceps, crush injury was induced in the left sciatic nerve. Thereafter, Cin was administered for 28 successive days. Weekly records were taken for sciatic functional index (SFI) measurements. Further assessments including electrophysiological and histomorphometric evaluations, gastrocnemius muscle wet weight measurements, and estimation of the serum total oxidant status were performed. According to the results, Cin could accelerate sciatic nerve recovery after crush injury, and the dose of 30 mg/kg/day of Cin had better impacts on SFI recovery, muscle mass ratio, and myelin content. The current research demonstrated that Cin positively affects peripheral nerve restoration. Therefore, Cin therapy could be considered as a potential treatment method for peripheral nerve regeneration and its functional recovery. However, more investigations are required to further validate the study results and evaluate the optimal dose of Cin.

Ketogenic Diet Potentiates Electrical Stimulation-Induced Peripheral Nerve Regeneration after Sciatic Nerve Crush Injury in Rats.

Recent findings indicate that the ketogenic diet (KD) is neuroprotective and electrical stimulation (ES) can improve functional recovery from peripheral nerve injury. However, it is not clear whether KD and ES play a synergistical role in the peripheral nerve recovery following injury. A KD consisting of a 3:1 ratio of fat to carbohydrate+protein is used and is coupled with ES treatment in a rat model of peripheral nerve crush injury. Neuromuscular recovery is evaluated by electromyography, and axonal regeneration and myelination by histological methods. The effects on insulin-like growth factor 1 (IGF-1) and IGF-1 receptor expression in peripheral nerve tissue, pre- and post-nerve injury, are also investigated. The combination of KD and ES synergistically increases muscle force in biceps femoris and gluteus maximus and prevents development of hypersensitivity in biceps femoris. It promotes peripheral nerve regeneration by increasing total axons, axon density, and axonal diameter, as well as myelin thickness and axon/fiber ratio. These effects are due to modulation of the IGF system as the treatment expression of IGF-1 and IGF-1 receptor in regenerated nerve tissue. The results establish that KD and ES promote peripheral nerve regeneration. Patients recovering from peripheral nerve injury may benefit from this combinational approach.

Effects of electroacupuncture on functional indices and pS6 expression following acute sciatic nerve crush injury in rats.

The aim of this study was to investigate the effect of electroacupuncture (EA) on recovery from acute sciatic nerve crush injury and the expression of pS6 in rats. A total of 108 adult male Sprague-Dawley rats were randomly divided into control, model, EA and EA+rapamycin (EA+Rapa) groups. 28 rats were allocated to undergo measurement of sciatic functional index (SFI); one rat in the EA+Rapa group was unsuccessfully modelled and excluded because of an anaesthetic problem. The remaining 80 rats were allocated to undergo Western blot detection of S6 ribosomal protein (pS6, ser240/244). The model was created by mechanical clamping of the sciatic nerve stem. EA stimulation at GB30 and ST36 for 15 min separately was applied once daily for rats in the EA and EA+Rapa groups. For rats in the EA+Rapa group, rapamycin, a mammalian target of rapamycin (mTor) pathway inhibitor, was injected intramuscularly (1 mg/kg/day) near the site of crush injury in the sciatic nerve and an equivalent amount of dimethyl sulfoxide was injected in the other three groups every other day. After treatment for 7, 14, 28 and 42 days post-operation, the SFI of 27 rats was obtained to evaluate recovery of motor function and five rats from each group per stage were used for Western blot detection of pS6. The SFI values showed that EA could significantly promote recovery of the injured sciatic nerve but rapamycin hindered the therapeutic effect of EA. Moreover, immunoblotting indicated that EA improved the expression of pS6 in the area of the sciatic nerve crush injury and local injection of rapamycin near the injured sciatic nerve decreased its expression. The pS6 level correlated with the extent of recovery of the injury. This study indicated that EA may activate the mTOR signalling pathway to enhance expression of pS6 and facilitate recovery following sciatic nerve crush injury.

Non-thermal plasma accelerates the healing process of peripheral nerve crush injury in rats.

The objective of this study was to evaluate the effect of non-thermal plasma (NTP) on the healing process of peripheral nerve crush injuries, which can occur during dental implant procedures. For this, a rat model of sciatic nerve crush injury (SNCI) was adopted. The rats were divided into three groups: non-nerve damage (non-ND), nerve damage (ND), and ND+NTP group. To evaluate the sciatic nerve (SN) function, the static sciatic index was calculated, and the muscle and SN tissues were subjected to a histologic analysis. The results showed that NTP effectively accelerated the healing process of SNCI in rats. In contrast to the ND group, which showed approximately 60% recovery in the SN function, the NTP-treated rats showed complete recovery. Histologically, the NTP treatments not only accelerated the muscle healing, but also reduced the edema-like phenotype of the damaged SN tissues. In the ND group, the SN tissues had an accumulation of CD68-positive macrophages, partially destroyed axonal fibers and myelinated Schwann cells. Conversely, in the ND+NTP group, the macrophage accumulation was reduced and an overall regeneration of the damaged axon fibers and the myelin sheath was accomplished. The results of this study indicate that NTP can be used for healing of injured peripheral nerves.

Metformin Enhances Functional Recovery of Peripheral Nerve in Rats with Sciatic Nerve Crush Injury

BackgroundThe aim of this study was to explore the effect of metformin by inducing autophagy for enhancing functional recovery of peripheral nerve in rats with sciatic nerve crush injury.Material/MethodAutophagy was determined by electron microscopy, immunofluorescence, and Western blot analysis. Motor function recovery was studied by the footprint intensity method. Axonal growth and regeneration were detected through Western blot while axonal remyelination was analysed through immunocytochemistry. Sensory and functional recovery were assessed by reflexive motor function analysis.ResultsThe present study deciphered the role of autophagy induction by metformin in motor functions and peripheral nerve regeneration following sciatic nerve crush injury in rats. The process was detected by measuring autophagosomes and the expression of microtubule-associated protein 1A/1B-light chain 3 upon metformin treatment of sciatic nerve crush-injured rats. Neurobehavioral recovery by metformin was tested by CatWalk gait analysis, and we quantified expression of myelin basic protein MBP and neurofilament NF200 at the damage sight by immunoblotting. In metformin-treated injured rats, autophagy was upregulated, by which the number of dead cells was decreased. Motor function was also recovered after metformin treatment, which was accompanied by upregulation of MBP and NF200 through autophagy induction. Surprisingly, the motor regenerative capability was reduced by treatment with 3-methyl adenine (an autophagy inhibitor) in nerve-injured rats.ConclusionsOur study revealed that pharmacological induction of autophagy has an important and active role in the regeneration of nerve and motor function regain.