Nerve Crush Injury In Rats Research Articles

Smooth Muscle Progenitor Cells Preserve the Erectile Function by Reducing Corporal Smooth Muscle Cell Apoptosis after Bilateral Cavernous Nerve Crush Injury in Rats.

Radical prostatectomy causes erectile dysfunction (ED) and irreversible morphologic changes, including induction of endothelial and smooth muscle cell (SMC) apoptosis in the corpus cavernosum (CC). The injection of smooth muscle progenitor cells (SPCs) thickens the vascular intima and has demonstrated therapeutic benefit in cardiovascular disease animal. Herein, we investigated the effect of SPCs on the recovery of erectile function (EF) in rat models with bilateral cavernous nerve (CN) injury. Twenty-four male Sprague-Dawley rats were randomized into sham, vehicle only, or SPC treatment groups. Rats in the SPC treatment and vehicle groups were subjected to bilateral CN injury before intracavernosal injection. Intracavernosal injections of SPCs increased all EF parameters at day 28 after injury and simultaneously reduced apoptosis of the SMCs. Ultrastructural analysis revealed that SPCs maintained the integrity of the CC by preserving the structure of the adherens junctions. Tracking transplanted SPCs labeled with EdU showed that transplanted SPCs remained in the CC 28 days after treatment. Intracavernosal SPC injection restored EF after bilateral CN injury by reducing SMC apoptosis, which favored the maintenance of the structure of adherens junctions and regulated the stability of corporal vessels. These findings demonstrate the therapeutic potential of SPCs for treating ED in humans.

Activation of autophagy in the retina after optic nerve crush injury in rats.

To investigate the activation of autophagy in rat retina after optic nerve crush (ONC) and evaluate its relationship with apoptosis of retinal ganglion cells (RGCs). The ONC model was established. Western blots were performed to investigate expression of p62, LC3 and Beclin-1. Transmission electron microscopy was performed to discover the autophagosomes in the retina after ONC. Immunohistochemistry was used to confirm the distribution of LC3. TUNEL was performed to confirm the relationship between autophagy and RGC apoptosis. p62/Beclin-1 ratio was declined shortly after ONC until to day 7 after ONC and then restored to a normal level at day 21. There was an opposite change in the LC3-II/LC3I ratio in the retina compared to the p62/Beclin-1 ratio. Increased autophagosomes were found after ONC using transmission electron microscopy, and most of the LC3-stained cells were colocalized with RGCs and Müller cells. More LC3-immunoreactive cells and apoptotic RGCs were found on day 7 following ONC. Possible activation of autophagy in RGCs after ONC; autophagy mainly occurred in RGCs and Müller cells, and the apoptosis of RGCs after ONC may be partly associated with autophagic activation.

Anti‐apoptotic and Neuroregenerative Effects of Soluble Protein Fraction of the Epidermal Secretion from the Arabian Gulf Catfish following Sciatic Nerve Crush Injury in Rats

Crush injuries (axonotmesis) occur from an acute traumatic compression of the nerve resulting in many different degrees of neural damage. Significant cell death and axon degeneration occur as a result of this damage, leading to permanent functional deficits. Previous clinical trials showed that catfish skin preparations (CSP) have an anti‐inflammatory and healing properties for diabetic foot ulcers, chronic back pain, and other neurological disorders. This study was designed to investigate the anti‐apoptotic effect of soluble protein fraction (SPF)‐Fraction C (FC) derived from CSP on the sciatic nerve crush injury. Assessment of peripheral axonal regeneration recovery and the neuroprotective properties of SPF‐FC on the spinal neurons was done following nerve injury and SPF‐FC treatment. Male Wistar rats (weight 200–250g) were randomly assigned into five groups: (I) SHAM, (II) CRUSH, (III) CRUSH+(1.5mg/kg) SPF‐FC, (IV) CRUSH+(3mg/kg) SPF‐FC, and (V) CRUSH+(4.5mg/kg) SPF‐FC. Rats underwent sciatic nerve crush surgery, followed by treatment with SPF‐FC administered intraperitoneally (IP) for two weeks, and sacrificed at the end of the fourth week. All animals were assessed for sensory and motor neurobehavioral tests throughout the four weeks. Peripheral axonal regeneration was assessed through whole mount staining technique of sciatic nerve using axonal markers (S100, NF, and MBP) and cell proliferation marker (Ki67). The neuroprotective properties of SPF‐FC treatment on the spinal cord neurons were assessed using Cresyl violet staining and immunohistochemistry of NeuN, while the apoptotic pathway was assessed using Western blot, immunohistochemistry, and TUNEL techniques. The results of this study showed that IP administration of different SPF doses significantly (p<0.05–0.001) improved the sensory and motor neurobehavioral functions recovery of the nerve‐injured groups. Visualization of sciatic nerve through whole mount staining revealed significant (p<0.000) increase in the expression levels of axonal regeneration recovery with CRUSH+(4.5mg/kg) SPF‐FC treatment. Moreover, the CRUSH+(4.5mg/kg) SPF‐FC treatments have neuroprotective effects on spinal cord neurons as was shown in Cresyl violet stained sections and NeuN‐immunoreactive neurons. Our results after employing WB, IHC, and TUNEL for the apoptotic pathway revealed that SPF‐FC treatments reduce neuronal cell death resulting from sciatic nerve crush injury. The data suggest that SPF‐FC reduces sensory and motor neurobehavioral deficits and enhances axonal regeneration recovery. Also, SPF‐FC alleviates the apoptotic and neurodegenerative modifications in spinal cord neurons. Therefore, SPF‐FC protects spinal neurons after peripheral nerve injury.Support or Funding InformationThis work was funded by the college of graduate studies, Kuwait university.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Qian-Zheng-San promotes regeneration after sciatic nerve crush injury in rats

Qian-Zheng-San, a traditional Chinese prescription consisting of Typhonii Rhizoma, Bombyx Batryticatus, Scorpio, has been found to play an active therapeutic role in central nervous system diseases. However, it is unclear whether Qian-Zheng-San has therapeutic value for peripheral nerve injury. Therefore, we used Sprague-Dawley rats to investigate this. A sciatic nerve crush injury model was induced by clamping the right sciatic nerve. Subsequently, rats in the treatment group were administered 2 mL Qian-Zheng-San (1.75 g/mL) daily as systemic therapy for 1, 2, 4, or 8 weeks. Rats in the control group were not administered Qian-Zheng-San. Rats in sham group did not undergo surgery and systemic therapy. Footprint analysis was used to assess nerve motor function. Electrophysiological experiments were used to detect nerve conduction function. Immunofluorescence staining was used to assess axon counts and morphological analysis. Immunohistochemical staining was used to observe myelin regeneration of the sciatic nerve and the number of motoneurons in the anterior horn of the spinal cord. At 2 and 4 weeks postoperatively, the sciatic nerve function index, nerve conduction velocity, the number of distant regenerated axons and the axon diameter of the sciatic nerve increased in the Qian-Zheng-San treatment group compared with the control group. At 2 weeks postoperatively, nerve fiber diameter, myelin thickness, and the number of motor neurons in the lumbar spinal cord anterior horn increased in the Qian-Zheng-San treatment group compared with the control group. These results indicate that Qian-Zheng-San has a positive effect on peripheral nerve regeneration.

Carnosine improves functional recovery and structural regeneration after sciatic nerve crush injury in rats

AimsPeripheral nerve injury represents a substantial clinical problem with insufficient or unsatisfactory treatment options. Current researches have extensively focused on the new approaches for the treatment of peripheral nerve injuries. Carnosine is a naturally occurring pleotropic dipeptide and has many biological functions such as antioxidant property. In the present study, we examined the regenerative ability of carnosine after sciatic nerve crush injury using behavioral, biochemical, histological and ultrastructural evaluations. Materials and methodsSeventy-two rats were divided into six groups including control, sham, crush and carnosine (10, 20 and 40 mg/kg) groups. Crush injury in left sciatic nerve was induced by a small haemostatic forceps. Carnosine was administered for 15 consecutive days after induction of crush injury. Sciatic functional index (SFI) was recorded weekly. Histopathological and ultrastructural evaluations were made using light and electron microscopes, respectively. Sciatic nerve tissue malondialdehyde (MDA), superoxide dismutase (SOD) and tumor necrosis factor-alpha (TNF-α) levels were measured. Gastrocnemius muscle weight was determined. Key findingsCarnosine at the doses of 20 and 40 mg/kg accelerated SFI recovery. Wallerian degeneration severity and myelinated fibers density, myelin sheath thickness and diameter as well as ultrastructural changes of myelinated axons were improved. It also recovered nerve tissue biochemical (MDA, SOD and TNF-α) changes induced by crush injury. Muscle weight ratio was reached to near normal values. Our results suggest a regenerative effect of carnosine. Inhibition of oxidative stress and inflammatory pathways, along with provocation of myelination and prevention of muscular atrophy might be involved in this effect of carnosine. SignificanceCarnosine treatment might be considered as a therapeutic agent for peripheral nerve regeneration and its functional recovery.

Tanshinone IIA attenuates nerve structural and functional damage induced by nerve crush injury in rats.

After peripheral nerve crush injury, the fibers of distal nerve segments gradually disintegrate, and axons regrow from the proximal nerve segment, eventually reaching the target organ. However, the axon regeneration is generally not sufficient for the recovery of neurological function, so drug therapy is necessary. In the current study, we explored the effect of Tanshinone IIA in nerve regeneration in a sciatic nerve crush injury model using Sprague Dawley rats. The rats were administered 45 mg/kg of Tanshinone IIA once daily. Motor behavior and tibialis anterior muscle mass were assessed, and histological analysis of the sciatic nerve and lumbar spinal cord were conducted. The results showed that the administration of Tanshinone IIA improved nerve growth and motor function, and resulted in a marked decrease of neuronal death. The findings of this exploratory study suggest that Tanshinone IIA alleviates injury and boosts regeneration after nerve crush injury in a rat model of sciatic nerve injury.

Neuroregenerative role of transplanted olfactory ensheathing cells in a model of sciatic nerve crush injury in rats: Histological study

Background: Olfactory ensheathing cells (OECs) are highly specialized glial cells that guide olfactory receptor axons from nasal mucosa to olfactory bulb. Olfactory ensheathing cells (OECs) are attractive candidates for transplantation-mediated repair of injured nervous system owing to their neuroregenerative properties.Aim of the work: To evaluate the neuroregenerative role of OECs in a model of sciatic nerve crush injury in rats.Materials and Methods: OECs were isolated from the olfactory mucosa of 15 male albino rats (100 gm). Thirty adult female albino rats (200-250 gm) were used and divided into three groups of 10 rats each. Group I (control group) underwent sham operation. Group II underwent crush injury of sciatic nerve. Group III underwent sciatic nerve crush injury then injected with single dose of 3×104 OECs at the lesion site. All rats were sacrificed after 3 weeks from the onset of the experiment.Results: Histological examination of sciatic nerves of group II rats showed discontinuity of nerve fibers with vacuolated axoplasm. OECs transplantation in group III revealed restoration of the normal histological architecture of the sciatic nerves. A significant decrease in the diameter of myelinated nerve fibers and myelin sheath thickness was recorded in group II compared to the control group. However, group III revealed a significant increase in the previous parameters compared to group II.Conclusions: Olfactory ensheathing cells (OECs) have neuroregenerative properties which might represent a new vision in human cell based therapy.

Possible role of antioxidative capacity of (-)-epigallocatechin-3-gallate treatment in morphological and neurobehavioral recovery after sciatic nerve crush injury.

OBJECTIVE This study examined the capacity of the major polyphenolic green tea extract (-)-epigallocatechin-3-gallate (EGCG) to suppress oxidative stress and stimulate the recovery and prompt the regeneration of sciatic nerve after crush injury. METHODS Adult male Wistar rats were randomly assigned to one of 4 groups: 1) Naïve, 2) Sham (sham injury, surgical control group), 3) Crush (sciatic nerve crush injury treated with saline), and 4) Crush+EGCG (sciatic nerve crush injury treated with intraperitoneally administered EGCG, 50 mg/kg). All animals were tested for motor and sensory neurobehavioral parameters throughout the study. Sciatic nerve and spinal cord tissues were harvested and processed for morphometric and stereological analysis. For the biochemical assays, the time points were Day 1, Day 7, Day 14, and Day 28 after nerve injury. RESULTS After sciatic nerve crush injury, the EGCG-treated animals (Crush+EGCG group) showed significantly better recovery of foot position and toe spread and 50% greater improvement in motor recovery than the saline-treated animals (Crush group). The Crush+EGCG group displayed an early hopping response at the beginning of the 3rd week postinjury. Animals in the Crush+EGCG group also showed a significant reduction in mechanical allodynia and hyperalgesia latencies and significant improvement in recovery from nociception deficits in both heat withdrawal and tail flick withdrawal latencies compared with the Crush group. In both the Crush+EGCG and Crush groups, quantitative evaluation revealed significant morphological evidence of neuroregeneration according to the following parameters: mean cross-sectional area of axons, myelin thickness in the sciatic nerve (from Week 4 to Week 8), increase of myelin basic protein concentration and gene expression in both the injured sciatic nerve and spinal cord, and fiber diameter to axon diameter ratio and myelin thickness to axon diameter ratio at Week 2 after sciatic nerve injury. However, the axon area remained much smaller in both the Crush+EGCG and Crush groups compared with the Sham and Naïve groups. The number of axons per unit area was significantly decreased in the Crush+EGCG and Crush groups compared with controls. Sciatic nerve injury produced generalized oxidative stress manifested as a significant increase of isoprostanes in the urine and decrease of the total antioxidant capacity (TAC) of the blood from Day 7 until Day 14. EGCG-treated rats showed significantly less increase of isoprostanes than saline-treated animals and also showed full recovery of TAC levels by Day 14 after nerve injury. In spinal cord tissue analysis, EGCG-treated animals showed induced glutathione reductase and suppressed induction of heme oxygenase 1 gene expression compared with nontreated animals. CONCLUSIONS EGCG treatment suppressed the crush-induced production of isoprostanes and stimulated the recovery of the TAC and was associated with remarkable alleviation of motor and sensory impairment and significant histomorphological evidence of neuronal regeneration following sciatic nerve crush injury in rats. The findings of this study suggest that EGCG can be used as an adjunctive therapeutic remedy for nerve injury. However, further investigations are needed to establish the antioxidative mechanism involved in the regenerative process after nerve injury. Only upregulation of glutathione reductase supports the idea that EGCG is acting indirectly via induction of enzymes or transcription factors.

The Histological Effects of Ozone Therapy on Sciatic Nerve Crush Injury in Rats.

Peripheral nerve injury is a common, important problem that lacks a definitive, effective treatment. It can cause neurologic deficits ranging from paresthesia to paralysis. This study evaluated the effect of ozone therapy on sciatic nerve crush injury in rats. Twenty-four male rats were divided into control sham surgery, sciatic nerve injury, and sciatic nerve injury with ozone groups (each n= 8). The sciatic nerve injury was inflicted via De Koning's crush-force method. The sciatic nerve injury group received medical air and the sciatic nerve injury ozone group received 0.7 mg/kg ozone. Sciatic nerve samples were obtained 4 weeks after injury. Vascular congestion, vacuolization, edema formation, S100 expression, and the thicknesses of the perineurium and endoneurium and diameter of the injured sciatic nerves were evaluated. The diameter of the sciatic nerve and thicknesses of the perineurium and epineurium were significantly greater in the sciatic nerve injury group (P< 0.05) and significantly less in the sciatic nerve injury with ozone group (P < 0.001). High S100 immunoreactivity was seen in the sciatic nerve injury group compared with the other 2 groups (P < 0.05). The distributions of vascular congestion and vacuolization were significantly less in the sciatic nerve injury with ozone group (P<0.05). Ozone therapy improved sciatic nerve injury recovery without causing an increase in fibrotic tissue. Ozone reduced fibrosis, vascular congestion, vacuolization, and edema in rodents. Ozone treatment might be used to assist in sciatic nerve injury.

Effects of alpha lipoic acid on motor function and antioxidant enzyme activity of nerve tissue after sciatic nerve crush injury in rats.

Background: Alpha lipoic acid (ALA) that is a strong antioxidant drug is tried for both protection and treatment of various diseases of central and peripheral nervous systems. Material and Methods: Protective effects of ALA on crush type peripheral nerve injury were evaluated. 28 Sprague-Dawley rats were divided into four groups: In Group 1, sciatic nerve was only explored. Sciatic nerve crush injury was performed after serum physiologic injection intraperitoneally in Group 2, and after ALA injection in Groups 3 and 4. In all subjects, Sciatic Functional Index (SFI) was calculated. All subjects were sacrificed 1 hour after injury in first three groups, and 48 hours after in Group 4. Nerve samples were taken. Superoxide dismutase, catalase and glutathione peroxidase activities were measured in nerve tissue. Results: Administration of ALA before injury provided significantly better SFI values and higher levels of antioxidant enzymes than control group. These effects were significantly prominent 48 hours after injury. Conclusion: ALA that was given before crush type peripheral nerve injury provided to decrease damage of the nerve. Specific mechanisms of this effect must be clarified and must be shown that it is whether effective when it is given after injury or not.

Global analysis of transcriptome in dorsal root ganglia following peripheral nerve injury in rats

Peripheral nervous system has intrinsic regeneration ability after injury, accompanied with the coordination of numerous cells, molecules and signaling pathways. These post-injury biological changes are complex with insufficient understanding. Thus, to obtain a global perspective of changes following nerve injury and to elucidate the mechanisms underlying nerve regeneration are of great importance. By RNA sequencing, we detected transcriptional changes in dorsal root ganglia (DRG) neurons at 0 h, 3 h, 9 h, 1 d, 4 d and 7 d following sciatic nerve crush injury in rats. Differentially expressed genes were then selected and classified into major clusters according to their expression patterns. Cluster 2 (with genes high expressed before 9 h and then down expressed) and cluster 6 (combination of cluster 4 and 5 with genes low expressed before 1 d and then up expressed) were underwent GO annotation and KEGG pathway analysis. Gene act networks were then constructed for these two clusters and the expression of pivotal genes was validated by quantitative real-time PCR. This study provided valuable information regarding the transcriptome changes in DRG neurons following nerve injury, identified potential genes that could be used for improving axon regeneration after nerve injury, and facilitated to elucidate the biological process and molecular mechanisms underlying peripheral nerve injury.

Cytidine 5'-diphosphocholine administration prevents peripheral neuropathic pain after sciatic nerve crush injury in rats.

BackgroundCytidine 5′-diphosphocholine (citicoline) has been shown to have beneficial effects in central nervous system injury as well as in motoric functional recovery after peripheral nerve injury. This study aimed to examine the effect of citicoline on prevention of neuropathic pain in a rat model of sciatic nerve crush injury.MethodsForty experimental rats were divided into four groups. In three groups, the right sciatic nerves were crushed in the mid-thigh region, and a gelatin sponge moistened with 0.4 or 0.8 mL of 100 µmol/L citicoline, or saline 0.4 mL in the control group, was applied. The fourth group of rats was sham-operated, ie the sciatic nerve was exposed with no crush. Functional assessments were performed 4 weeks after crush injury. von Frey filaments (100 g threshold) were used to assess neuropathic pain. In addition, the sciatic functional index and extensor postural thrust (EPT) tests were used to assess motoric function.ResultsThe crush/citicoline 0.4 mL group had a lower percentage of pain (23.53%, n=17) compared with the crush/saline group (53.33%, n=15, P<0.005). The crush/citicoline 0.4 mL group also showed better motoric recovery, as seen in stronger EPT results (P<0.001). However, the sciatic functional index analysis did not show significant differences between groups (P=0.35). The crush/citicoline 0.8 mL group showed a higher percentage of pain (66.67%, n=18) and less EPT recovery. These results may be explained by more severe nerve injury due to compression with a larger administered volume.ConclusionIn situ administration of 0.4 mL of 100 µmol/L citicoline prevents the occurrence of neuropathic pain and induces motoric recovery, evaluated by EPT test, 4 weeks after sciatic nerve injury.

Autophagy Promotes Peripheral Nerve Regeneration and Motor Recovery Following Sciatic Nerve Crush Injury in Rats.

Autophagy maintains cellular homeostasis by stimulating the lysosomal degradation of cytoplasmic structures, including damaged organelles and dysfunctional proteins. The role of autophagy in the renewal and regeneration of injured peripheral nerves remains poorly understood. The current study investigated the role of autophagy in peripheral nerve regeneration and motor function recovery following sciatic nerve crush injury in rats by stimulating or suppressing autophagy and detecting the presence of autophagosomes and LC3-II expression by electron microscopy and Western blotting, respectively. Neurobehavioral function was tested by CatWalk gait analysis 1, 2, 3, and 6 weeks after injury, and the expression of neurofilament (NF)-200 and myelin basic protein (MBP) at the injury site was examined by immunocytochemistry. Apoptosis at the lesion site was determined by the terminal deoxynucleotidyl transferase dUTP nick end labeling assay. Treatment of injured rats with the autophagy inducer rapamycin increased the number of autophagosomes and LC3-II expression while reducing the number of apoptotic cells at the lesion; this was associated with an upregulation of MBP and NF-200 expression and increased motor function recovery as compared to sham-operated rats and those that were subjected to crush injury but untreated. The opposite effects were observed in rats treated with the autophagy inhibitor 3-methyladenine. These data indicate that the modulation of autophagy in peripheral nerve injury could be an effective pharmacological approach to promote nerve regeneration and reestablish motor function.

The Effect of Memantine on Functional Recovery of the Sciatic Nerve Crush Injury in Rats.

Following severe peripheral nerve injury (PNI), regeneration is often insufficient and functional recovery is incomplete. In this regard, glutamate N-methyl-D-aspartate (NMDA) receptor antagonist such as Memantine have been shown to have neuroprotective effects. We evaluated the effects of Memantine against sciatic nerve crush injury in male Wistar Rats. Memantine or vehicle was given parenteraly to rats for 7 days postoperative. In Memantine treatment groups, a single dose of agent (5 and 10 mg/kg) was administered daily. The control group was given vehicle in the same manner. The rats were subjected to crush injury in the left sciatic nerve with non-serrated clamp for 30 seconds. Behavioural, electrophysiological and morphological alterations were evaluated during the experimental period. Results showed that Memantine has no significant effect on regeneration process rate and functional recovery quality. In the sciatic functional index (SFI) test no significant difference was observed between Memantine treatment groups (5 and 10 mg/ kg) at any week. Since the major neuroprotective effect of Memantine is due to its protective activity against NMDA receptormediated excitotoxicity, it seems that glutamate excitotoxicity is less important in motor impairment due to sciatic nerve crush injury. It is clear that more research is needed to confirm these findings.

Curcumin upregulates S100 expression and improves regeneration of the sciatic nerve following its complete amputation in mice.

The repair of peripheral nerve injury after complete amputation is difficult, and even with anastomosis, the rapid recovery of nerve function remains challenging. Curcumin, extracted from plants of the genus Curcuma, has been shown to have anti-oxidant and anti-inflammatory properties and to improve sciatic nerve crush injury in rats. Here, we determined whether curcumin had neuroprotective effects following complete peripheral nerve amputation injury. BALB/c mice underwent complete sciatic nerve amputation, followed by an immediate epineurium anastomosis. Mice were intragastrically administered curcumin at doses of 40 (high), 20 (moderate), and 10 mg/kg/d (low) for 1 week. We found that myelin in the mice of the high- and moderate-dose curcumin groups appeared with regular shape, uniform thickness, clear boundary, and little hyperplasia surrounding the myelin. High and moderate doses of curcumin markedly improved both action potential amplitude of the sciatic nerves and the conduction velocity of the corresponding motor neurons, and upregulated mRNA and protein expression of S100, a marker for Schwann cell proliferation, in L4-6 spinal cord segments. These results suggest that curcumin is effective in promoting the repair of complete sciatic nerve amputation injury and that the underlying mechanism may be associated with upregulation of S100 expression.

The Effects of Exercise Intensity and Initial Timing on Functional Recovery after Sciatic Nerve Crush Injury in Rats

The Effects of Exercise Intensity and Initial Timing on Functional Recovery after Sciatic Nerve Crush Injury in Rats

Nimodipine-mediated re-myelination after facial nerve crush injury in rats

This study aimed to investigate the mechanism of nimodipine-mediated neural repair after facial nerve crush injury in rats. Adult Sprague–Dawley rats were divided into three groups: healthy controls, surgery alone, and surgery plus nimodipine. A facial nerve crush injury model was constructed. Immediately after surgery, the rats in the surgery plus nimodipine group were administered nimodipine, 6mg/kg/day, for a variable numbers of days. The animals underwent electromyography (EMG) before surgery and at 3, 10, or 20days after surgery. After sacrifice, nerve samples were stained with hematoxylin and eosin (H&E) and luxol fast blue. The EMG at 20days revealed an apparent recovery of eletroconductivity, with the surgery plus nimodipine group having a higher amplitude and shorter latency time than the surgery only group. H&E staining showed that at 20days, the rats treated with nimodipine had an obvious recovery of myelination and reduction in the number of infiltrating cells, suggesting less inflammation, compared with the rats in the surgery only group. Luxol fast blue staining was relatively even in the surgery plus nimodipine group, indicating a protective effect against injury-induced demyelination. Staining for S100 calcium-binding protein B (S-100β) was not evident in the surgery alone group, but was evident in the surgery plus nimodipine group, indicating that nimodipine reversed the damage of the crush injury. After a facial nerve crush injury, treatment with nimodipine for 20days reduced the nerve injury by mediating remyelination by Schwann cells. The protective effect of nimodipine may include a reduction of inflammation and an increase in calcium-binding S-100β protein.

Electrical stimulation influences satellite cell differentiation after sciatic nerve crush injury in rats.

Electrical stimulation is often used to prevent muscle atrophy and preserve contractile function, but its effects on the satellite cell population after nerve injury are not well understood. In this study we aimed to determine whether satellite cell differentiation is affected by electrical stimulation after nerve crush. The sciatic nerves of Sprague-Dawley (SD) rats were crushed. Half of the injured rats received daily electrical stimulation of the gastrocnemius muscle, and the others did not. Tests for detecting paired box protein 7 (Pax7), myogenic differentiation antigen (MyoD), embryonic myosin heavy chain (eMyHC), and force production were performed 2, 4, and 6 weeks after injury. More Pax7+/MyoD+ nuclei in stimulated muscles were observed than in non-stimulated muscles. eMyHC expression was elevated in stimulated muscles and correlated positively with enhanced force production. Increased satellite cell differentiation is correlated with preserved muscle function in response to electrical stimulation after nerve injury.

Dexamethasone enhanced functional recovery after sciatic nerve crush injury in rats.

Dexamethasone is currently used for the treatment of peripheral nerve injury, but its mechanisms of action are not completely understood. Inflammation/immune response at the site of nerve lesion is known to be an essential trigger of the pathological changes that have a critical impact on nerve repair and regeneration. In this study, we observed the effects of various doses of dexamethasone on the functional recovery after sciatic nerve crush injury in a rat model. Motor functional recovery was monitored by walking track analysis and gastrocnemius muscle mass ratio. The myelinated axon number was counted by morphometric analysis. Rats administered dexamethasone by local intramuscular injection had a higher nerve function index value, increased gastrocnemius muscle mass ratio, reduced Wallerian degeneration severity, and enhanced regenerated myelinated nerve fibers. Immunohistochemical analysis was performed for CD3 expression, which is a marker for T-cell activation, and infiltration in the sciatic nerve. Dexamethasone-injected rats had fewer CD3-positive cells compared to controls. Furthermore, we found increased expression of GAP-43, which is a factor associated with development and plasticity of the nervous system, in rat nerves receiving dexamethasone. These results provide strong evidence that dexamethasone enhances sciatic nerve regeneration and function recovery in a rat model of sciatic nerve injury through immunosuppressive and potential neurotrophic effects.

The double-edged sword: effects of pregabalin on experimentally induced sciatic nerve transection and crush injury in rats

Aim: The aim of this study was to research the effects of pregabalin on experimentally induced peripheral nerve crush injuries in rats. Material and method: Forty-two adult female Wistar albino rats were divided into seven groups: 1st group: healthy; 2nd group: axonotmesis control; 3rd group: anastomosis control; 4th group: axonotmesis+30 mg/kg of pregabalin; 5th group: axonotmesis+60 mg/kg of pregabalin; 6th group: anastomosis+30 mg/kg of pregabalin; 7th group: anastomosis+60 mg/kg of pregabalin. Evaluation of the sciatic functional index (SFI) was performed one day before and on days 7, 14, 21, and 28 following surgery. The right sciatic nerves of all animals were examined histopathologically and molecularly. Results: After 28 days post-injury, the histopathological regeneration in peripheral nerve injuries for pregabalin 30 mg/kg treated groups was significantly better than that of the control groups. Also the SFI increases and TGF-β gene expression up-regulation were significantly better in pregabalin 30 mg/kg treated groups. Conclusion: The histopathological, functional and molecular data suggest that pregabalin 30 mg/kg treatment in axonotmesis and anostomosis groups improves nerve regeneration and increases SFI in peripheral nerve injuries by activating antiinflammatory cytokine TGF-β1.