Functional recovery after facial and sciatic nerve crush injury in the rat

OBJECTIVES: To systematically record rat facial nerve recovery following crush injury to the main trunk with respect to ocular and vibrissial function and to compare the rates of facial and sciatic nerve recovery from crush injury in the same animals. This serves as a means of validating the functional parameters of facial nerve recovery against the well-known measure of hind limb function, the Sciatic Function Index. METHODS: The main trunk of the facial nerve and the proximal segment of the sciatic nerve were exposed in all animals. Both nerves were subjected to standardized crush injury and subsequent daily functional testing. After a plateau of functional recovery was achieved, the animals were killed, and the distances between the sites of injury and the end musculature were measured, which allowed determination and comparison of recovery rates in both systems. RESULTS: All crush injuries resulted in loss of electrical conductivity, as proven by intraoperative proximal nerve stimulation. Recovery of ocular and vibrissial motor function occurred starting at postoperative day (POD) 9 and continuing through POD 20. Hind limb function returned later (POD 14-34); however, when corrected for distance, the sciatic recovery rate (2.26 mm/d) appeared to match that of the facial nerve (1.5-2.4 mm/d). CONCLUSIONS: Recovery after facial nerve crush injury follows a predictable time course, and the rate of recovery is consistent with that of sciatic nerve injury. Return of the blink reflex, loss of vibrissial fibrillations, and return of vibrissial sweeping function appear to be internally consistent functional measures of facial recovery. These quantitative measures will be useful for future facial nerve manipulation studies.     

Dehydroepiandrosterone as an enhancer of functional recovery following crush injury to rat sciatic nerve

This study was designed to investigate the effect of dehydroepiandrosterone (DHEA) on the recovery of the rat sciatic nerve following crush injury. A standard hemostat system was used to create the injury, with a length of 1.5 mm in three groups of 18 animals each. In group I, the crush injury was applied without any treatment. In groups II and III, vehicle (ethylene glycol) and DHEA solutions were injected subepineurally 30 min following the crush injury. Sciatic function index (SFI), toe contracture measurement, gastrocinemius muscle weight, total number of myelinated fibers, fiber diameters, myelin thickness, and axon/fiber cross-sectional ratio were measured at 3, 6, and 12 weeks. The SFI values in the DHEA group showed a faster return to normal values confirmed at 3 and 6 weeks (P < 0.05). The number of myelinated fibers and fiber diameters at 6 and 12 weeks were significantly higher in the DHEA group (P < 0.05). In this study, the subepineural injection of DHEA following crush injury was found to enhance functional recovery of the rat sciatic nerve.     

The effect of Riluzole on functional recovery of locomotion in the rat sciatic nerve crush model

European Journal of Trauma and Emergency Surgery - Peripheral nerve injury (PNI) is common disorder that represents more than 3&nbsp;% of all traumatic injury cases. One type of PNI, sciatic...     

Methodological evaluation to analyze functional recovery after sciatic nerve injury

The Basso, Bresnahan and Beattie (BBB) locomotor scale has not been tested to evaluate functional consequences of peripheral nerve lesions. Alternative methods to evaluate animal functional recovery after sciatic nerve injury are desirable. Male Wistar rats had a right sciatic nerve segment exposed and were divided in three experimental groups: Sham (wound open, 10 min), Sham-device (nerve segment between crushing device, 10 min), and Crush-force (nerve crushing load of 15,000 g/1,000 mm Hg/mm(2), 10 min). Animals were evaluated preoperatively, 1, 7, 14, 21, and 28 days after procedure by calculation of Sciatic Functional Index (SFI), BBB score and open arena exploratory activity. The primary findings of the present study were (1) the SFI calculated by either DeMedinaceli, Carlton and Goldberg, and Bain formulae were highly correlated; (2) the BBB score evaluation was highly correlated with the SFI; (3) the BBB motor scale was able to detect functional impairments not recognized by the SFI; and (4) open arena exploratory activity was a poor method to detect sciatic nerve impairment. In conclusion, the BBB prescribed functional deficits on the sham-device and crush-force groups even when the SFI indicated full recovery. This greater sensitivity may prove useful when comparing new therapeutic approaches to nerve regeneration.     

Effect of glial growth factor on functional recovery of peripheral nerve after crush injury

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Extracts obtained from predegenerated nerves improve functional recovery after sciatic nerve transection

Gap injuries of peripheral nerves, resulting from trauma or neurosurgical procedures, presage badly, for the presence of the distal stump of the nerve seems to be indispensable for regeneration. The standard grafting method requires a lesion of a healthy nerve, and therefore various substitutional materials are under consideration. The aim of the present work was to examine the recovery of rat sciatic nerves after supplying 10-mm-long gaps with an autologous connective-tissue chambers filled with fibrin only or fibrin and various neuroactive substances (brain-derived neurotrophic factor (BDNF), extracts from predegenerated or non-predegenerated nerves). The nerves were allowed to regenerate for 16 weeks. Recovery was measured functionally using the sciatic functional index, and by comparing the weight ratios of calf muscles. The histologic features of regeneration were assessed by counting the number of acetylcholinesterase-positive nerve fibers present inside implanted chambers. We found that chambers filled with fibrin and predegenerated peripheral nerve extracts or BDNF supported functional nerve regeneration much more strongly than chambers filled with fibrin only or fibrin and non-predegenerated peripheral nerve extracts. We conclude that autologous connective-tissue chambers filled with fibrin and predegenerated peripheral nerve extracts or BDNF seem to be a promising tool in peripheral nerve gap injury treatment, with likely clinical implications.     

Neural cell transplantation effects on sciatic nerve regeneration after a standardized crush injury in the rat

The goal of the present study was to assess whether in vitro-differentiated N1E-115 cells supported by a collagen membrane would enhance rat sciatic nerve regeneration after a crush injury. To set up an appropriate experimental model for investigating the effects of neural cell transplantation, we have recently described the sequence of functional and morphologic changes occurring after a standardized sciatic nerve crush injury with a nonserrated clamp. Functional recovery was evaluated using the sciatic functional index, the static sciatic index, the extensor postural thrust, the withdrawal reflex latency, and ankle kinematics. In addition, histomorphometric analysis was carried out on regenerated nerve fibers by means of the 2D-disector method. Based on the results of the EPT and of some of the ankle locomotor kinematic parameters analyzed, the hypothesis that N1E-115 cells may enhance nerve regeneration is partially supported although histomorphometry disclosed no significant difference in nerve fiber regeneration between the different experimental groups. Therefore, results suggest that enrichment of equine type III collagen membrane with the N1E-115 cellular system in the rat sciatic nerve crush model may support recovery, at least in terms of motor function. The discrepancy between functional and morphological results also suggests that the combined use of functional and morphological analysis should be recommended for an overall assessment of recovery in nerve regeneration studies.     

Effects of intrathecal administration of FK506 after sciatic nerve crush injury

Although various administration routes of FK506 have been published, intrathecal administration of FK506 has not previously been reported in the literature. A daily dose of 0.05 mg/kg of FK506 was given (a small dose compared with those reported in the available literature). The authors used this small dose to obtain lower immunosuppression and neurotoxicity, and a higher axonal regeneration rate. A total number of 40 female Wistar rats were used and randomly divided into four groups: control, sham, FK506-treated, and vehicle-treated. Sciatic nerve regeneration was evaluated by walking track analysis, an electrostimulation test, and light microscopic evaluation. There was a statistically significant difference ( P < 0.05) between FK506-treated and vehicle-treated groups at the end of 6 weeks according to both the walking track analysis and the electrostimulation test. Comparing the stimulus thresholds of the sham and FK506-treated group, no significant difference ( P > 0.05) was observed. Evaluation of the data revealed that FK506 had a beneficial effect on sciatic nerve regeneration.     

Correlation between functional index and morphometry to evaluate recovery of the rat sciatic nerve following crush injury: experimental study

An experimental study on the correlation between functional and morphologic recovery of crushed sciatic nerves was carried out in rats. The sciatic nerve of 33 rats, divided into three groups, was submitted to controlled crushing injury on a 5-mm long segment, in a universal testing machine for 10 min with three different loads (100, 500, and 15,000 g, respectively). Functional recovery was evaluated, using a modified sciatic functional index (SFI) at weekly intervals up to the 60th postoperative day, at which time, the animals were sacrificed for histologic and morphometric studies of the nerves. Results were compared with those of normal untouched nerves and nerves submitted to segmentary resection without repair. Initial loss of function was observed in all animals with crush injury, but recovery to a nearly normal SFI occurred after progressively longer intervals (25, 39, and 53 days), as a function of load. Nerve-fiber density was increased in the groups submitted to lower loads, but statistically significantly decreased in the animals submitted to the 15,000-g crush. The authors conclude that the SFI is directly correlated with nerve-fiber density and, therefore, is an adequate tool for evaluating sciatic functional deficiency in the rat.     

Effects of tobacco smoke on recovery after nerve crush injury in rats

The effects of tobacco smoke on nerve healing after crush injury was studied in a rat model. Thirty-six animals were randomized equally into smoke-exposed or nonsmoke-exposed groups. Two nerve crush injuries were performed on the right posterior tibial nerve of each animal at 4-week intervals to mimic a sustained or chronic nerve injury. Recovery of the two groups was assessed with walking track analysis and nerve histomorphometry. There was no difference in the rate of nerve recovery based on walking track analysis in the smoke-exposed animals compared with nonexposed animals. The study also failed to demonstrate any significant difference between the two groups as assessed by histomorphometric criteria.     

Raman spectroscopy and sciatic functional index (SFI) after low-level laser therapy (LLLT) in a rat sciatic nerve crush injury model

Lasers in Medical Science - Axonotmesis causes sensorimotor and neurofunctional deficits, and its regeneration can occur slowly or not occur if not treated appropriately. Low-level laser therapy...     

嗅鞘细胞促进大鼠坐骨神经损伤后神经功能恢复

目的研究嗅鞘细胞（Olfactory ensheathing cells,OECs）移植对大鼠坐骨神经损伤后神经再生恢复的作用。方法取SD大鼠40只随机分成对照生理盐水（SAL）组和实验（OECs）组,予离断坐骨神经后直接予神经外膜缝合修复,在神经缝合处周围充填可吸收的明胶海绵,SAL组和OECs组明胶海绵内分别给予SAL和体外培养纯化的OECs;术后4、12周分别行大体观察,电生理检查和组织学检查。结果术后4、12周,SAL组和OECs组修复神经均有不同程度恢复,OECs组在运动神经传导速度、神经肌肉动作电位幅度和直径数据上有优于SAL组,但统计学上未见明显差异,而在有髓神经纤维数目方面明显优于SAL组（P〈0.05）。结论在本实验条件下,嗅鞘细胞（OECs）对大鼠坐骨神经损伤后的神经功能恢复有部分的促进作用。     

Osteoprotegerin ameliorates sciatic nerve crush induced bone loss.

This study examines the ability of osteoprotegerin (OPG) to prevent the local bone resorption caused by sciatic nerve damage. Sixty-five 18-week-old male mice were assigned to one of six groups (n = 10-11/group). A baseline control group was sacrificed on day zero of the 10-day study. The remaining groups were placebo sham operated, placebo nerve crush (Plac NC) operated, 0.1 mg/kg/day OPG + nerve crush (LOW), 0.3 mg/kg/day OPG + nerve crush (MED), and 1.0 mg/kg/day OPG + nerve crush (HI). Nerve crush or sham operations were performed on the right leg. The left leg served as a contralateral control to the nerve crushed (ipsilateral) leg. The difference in mass between the right and left femur and tibia was examined. Additionally, quantitative histomorphometry was performed on the right and left femur and tibia diaphyses. Nerve crush resulted in a significant loss of bone mass in the ipsilateral side compared to the contralateral side. Bone mass for the ipsilateral bones of the Plac NC group were significantly reduced by 3.8% in the femur and 3.5% in the tibia compared to the contralateral limb. The percent diminution was reduced for OPG treated mice compared to the Plac NC group for both the femur and tibia. In the femur, the percent reduction of ipsilateral bone mass was reduced to 1.0% (LOW), 1.3% (MED) and 1.6% (HI) compared to the contralateral limb. In the tibia, loss of bone mass in the ipsilateral limb was reduced to 1.4% (LOW), 1.4% (MED), and 2.4% (HI) compared to the contralateral. OPG also decreased the amount of tibial endocortical resorption compared to the Plac NC group. In summary, OPG mitigated bone loss caused by damage to the sciatic nerve.     

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.     

犬化学去细胞神经同种异体移植的实验研究

目的以化学去细胞同种坐骨神经移植修复犬坐骨神经的长段缺损，观察其功能恢复及神经再生。方法15犬分成去细胞同种神经组(实验组)6犬、自体神经组(对照组Ⅰ)6犬、新鲜同种神经组(对照组Ⅱ)3犬。右侧坐骨神经造成5．0cm长缺损，以上述三种移植物桥接修复。术后6个月行步态分析、神经电生理及神经再生观察。结果实验组和对照组Ⅰ在运动功能恢复，踝关节运动步态，小腿二头肌运动诱发电位、感觉诱发电位，移植段内新生轴突、血管及雪旺细胞，远端胫神经内有髓神经纤维及靶肌肉运动终板等方面非常相似。对照组Ⅱ神经功能始终无恢复，移植段被吸收。结论化学去细胞同种神经移植物修复犬粗大长段神经缺损时不会被宿主排斥和吸收，其近期功能恢复及神经再生与自体神经移植无明显差别。     

Simvastatin improves morphological and functional recovery of sciatic nerve injury in Wistar rats

AimThe purpose of this work is to investigate the effects of simvastatin on sciatic nerve regeneration in male Wistar Rats.Materials and methodsForty animals were allocated into four groups: (1) control (C); (2) control + simvastatin (CS); (3) lesioned animals + sterile PBS (LC) and (4) lesioned animals + simvastatin (LS). Lesioned animals were submitted to crushing lesion of right sciatic nerve. Simvastatin (20 mg/kg/day, i.p.) was administered for five days. Footprints were obtained weekly for evaluation of functional locomotor recovery by means of the Sciatic Function Index (SFI). Blood samples were obtained weekly for quantifying circulating leukocytes. Animals were sacrificed after 21 days for histological analyses of sciatic nerve and spleen.ResultsLS Animals presented increased SFI scores, decreased areas of oedema and mononuclear cell infiltration during Wallerian degeneration and nerve regeneration (7,14 and 21 days; P < 0.05). Spleen weight and white pulp areas was increased in LC animals after 21 days. Increased numbers of circulating neutrophils were observed in simvastatin treated animals (CS e LS) at seven, 14 and 21 days, compared to non-treated groups (C and LC).ConclusionThe study suggests that simvastatin accelerates the morphological and functional recovery process of the peripheral nervous system interfering with innate and acquired immunity.