Neuroprotective Effects of Ozone Therapy After Sciatic Nerve Cut Injury.

A number of antioxidants have been used to treat peripheral nerve injury. However, there are few definitive experimental studies of ozone therapy for peripheral nerve cut injury. We aimed to examine the effects of mild level ozone therapy on sciatic nerve regeneration. One hundred adult male Wistar albino rats were randomly divided into four groups: group 1 (n=20) no cut injury or therapy; group 2 (n=20) sham; group 3 (n=30) nerve cut injury, no therapy; group 4 (n=30) nerve cut injury and ozone therapy. Sciatic functional index (SFI) and withdrawal reflex (WDR) were measured for all groups before nerve cut, at postoperative day 1, and at weeks 2, 4, 6 and 8. More myelinated (M) nerve fibers were observed after nerve cut injury in the ozone-therapy group. Significant differences were seen in plasma SOD (superoxide dismutase), CAT (catalase) and GPx (glutathione peroxidase) activities (p<0.05), and significant functional improvement was observed at postoperative weeks 2 and 4 (p<0.05) after ozone treatment. This is the first study conducted for the purpose of examining the effects of ozone therapy on sciatic nerve cut injury.

Manual stimulation of the whisker pad after hypoglossal-facial anastomosis (HFA) using a Y-tube conduit does not improve recovery of whisking function.

Facial nerve injury is a common clinical trauma involving long-term functional deficits with facial asymmetry leading to associated psychological issues and social hardship. We have recently shown that repair by hypoglossal-facial or facial-facial nerve surgical end-to-end anastomosis and suture [hypoglossal-facial anastomosis (HFA) or facial-facial anastomosis (FFA)] results in collateral axonal branching, polyinnervation of neuromuscular junctions (NMJs) and poor function. We have also shown that another HFA repair procedure using an isogenic Y-tube (HFA + Y-tube) and involving a 10-mm gap reduces collateral axonal branching, but fails to reduce polyinnervation. Furthermore, we have previously demonstrated that manual stimulation (MS) of facial muscles after FFA or HFA reduces polyinnervation of NMJs and improves functional recovery. Here, we examined whether HFA + Y-tube and MS of the vibrissal muscles reduce polyinnervation and restore function. Isogenic Y-tubes were created using abdominal aortas. The proximal hypoglossal nerve was inserted into the long arm and sutured to its wall. The distal zygomatic and buccal facial nerve branches were inserted into the two short arms and likewise sutured to their walls. Manual stimulation involved gentle stroking of the vibrissal muscles by hand mimicking normal whisker movement. We evaluated vibrissal motor performance using video-based motion analysis, degree of collateral axonal branching using double retrograde labeling and the quality of NMJ reinnervation in target musculature using immunohistochemistry. MS after HFA + Y-tube reduced neither collateral branching, nor NMJ polyinnervation. Accordingly, it did not improve recovery of function. We conclude that application of MS after hypoglossal-facial nerve repair using an isogenic Y-tube is contraindicated: it does not lead to functional recovery but, rather, worsens it.

Intrinsic and therapeutic factors determining the recovery of motor function after peripheral nerve transection.

Insufficient recovery after peripheral nerve injury has been attributed to (i) poor pathfinding of regrowing axons, (ii) excessive collateral axonal branching at the lesion site and (iii) polyneuronal innervation of the neuromuscular junctions (NMJ). The facial nerve transection model has been used initially to measure restoration of function after varying therapies and to examine the mechanisms underlying their effects. Since it is very difficult to control the navigation of several thousand axons, efforts concentrated on collateral branching and NMJ-polyinnervation. Treatment with antibodies against trophic factors to combat branching improved the precision of reinnervation, but had no positive effects on functional recovery. This suggested that polyneuronal reinnervation--rather than collateral branching--may be the critical limiting factor. The former could be reduced by pharmacological agents known to perturb microtubule assembly and was followed by recovery of function. Because muscle polyinnervation is activity-dependent and can be manipulated, attempts to design a clinically feasible therapy were performed by electrical stimulation or by soft tissue massage. Electrical stimulation applied to the transected facial nerve or to paralysed facial muscles did not improve vibrissal motor performance and failed to diminish polyinnervation. In contrast, gentle stroking of the paralysed muscles (vibrissal, orbicularis oculi, tongue musculature) resulted in full recovery of function. This manual stimulation was also effective after hypoglossal-facial nerve suture and after interpositional nerve grafting, but not after surgical reconstruction of the median nerve. All these findings raise hopes that clinically feasible and effective therapies could be soon designed and tested.

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.