Nerve Transection Repair Research Articles

Regenerative potential of human dental pulp stem cells in the treatment of stress urinary incontinence: In vitro and in vivo study.

ObjectivesTo evaluate the regenerative potential of human dental pulp stem cells (hDPSCs) in an animal model of stress urinary incontinence (SUI). SUI, an involuntary leakage of urine, is due to physical stress involving an increase in bladder pressure and a damage of external urethral sphincter affecting muscles and nerves. Conventional therapies can only relieve the symptoms. Human DPSCs are characterized by peculiar stemness and immunomodulatory properties and might provide an alternative tool for SUI therapy.Materials and methodsIn vitro phase: hDPSCs were induced towards the myogenic commitment following a 24 hours pre‐conditioning with 5‐aza‐2′‐deoxycytidine (5‐Aza), then differentiation was evaluated. In vivo phase: pudendal nerve was transected in female rats to induce stress urinary incontinence; then, pre‐differentiated hDPSCs were injected in the striated urethral sphincter. Four weeks later, urethral sphincter regeneration was assayed through histological, functional and immunohistochemical analyses.ResultsHuman DPSCs were able to commit towards myogenic lineage in vitro and, four weeks after cell injection, hDPSCs engrafted in the external urethral sphincter whose thickness was almost recovered, committed towards myogenic lineage in vivo, promoted vascularization and an appreciable recovery of the continence. Moreover, hDPSCs were detected within the nerve, suggesting their participation in repair of transected nerve.ConclusionsThese promising data and further investigations on immunomodulatory abilities of hDPSCs would allow to make them a potential tool for alternative therapies of SUI.

Nerve transection repair using laser-activated chitosan in a rat model.

Cranial nerve transection during head and neck surgery is conventionally repaired with microsuture. Previous studies have demonstrated recovery with laser nerve welding (LNW), a novel alternative to microsuture. LNW has been reported to have poorer tensile strength, however. Laser-activated chitosan, an adhesive biopolymer, may promote nerve recovery while enhancing the tensile strength of the repair. Using a rat posterior tibial nerve injury model, we compared four different methods of nerve repair in this pilot study. Animal study. Animals underwent unilateral posterior tibial nerve transection. The injury was repaired by potassium titanyl phosphate (KTP) laser alone (n = 20), KTP + chitosan (n = 12), microsuture + chitosan (n = 12), and chitosan alone (n = 14). Weekly walking tracks were conducted to measure functional recovery (FR). Tensile strength (TS) was measured at 6 weeks. At 6 weeks, KTP laser alone had the best recovery (FR = 93.4% ± 8.3%). Microsuture + chitosan, KTP + chitosan, and chitosan alone all showed good FR (87.4% ± 13.5%, 84.6% ± 13.0%, and 84.1% ± 10.0%, respectively). One-way analysis of variance was performed (F(3,56) = 2.6, P = .061). A TS threshold of 3.8 N was selected as a control mean recovery. Three groups-KTP alone, KTP + chitosan, and microsuture + chitosan-were found to meet threshold 60% (95% confidence interval [CI]: 23.1%-88.3%), 75% (95% CI: 46.8%-91.1%), and 100% (95% CI: 75.8%-100.0%), respectively. In the posterior tibial nerve model, all repair methods promoted nerve recovery. Laser-activated chitosan as a biopolymer anchor provided good TS and appears to be a novel alternative to microsuture. This repair method may have surgical utility following cranial nerve injury during head and neck surgery. NA Laryngoscope, 127:E253-E257, 2017.

Axonal fusion via conduit-based delivery of hydrophilic polymers.

Hydrophilic polymers have been shown to improve physiologic recovery following repair of transected nerves with microsutures. Our study was designed to combine hydrophilic polymer therapy with nerve tubes (NT) to enhance polymer delivery to the site of nerve injury. Using a rat sciatic nerve injury model, a single transection injury was repaired in an end-to-end fashion with NT + polyethylene glycol (PEG) to NT alone. Compound action potentials (CAPs) were recorded before nerve transection and after repair. Behavioral testing was performed for 5weeks. PEG therapy restored CAPS in all, but one, animals, while no CAPS were recorded in animals not receiving PEG. Behavioral nerve function was measured using the standardized functional assessment technique and foot fault asymmetry scores (FF). FF scores were improved for the PEG therapy groups on postoperative days 7, 14, and 21. However, after expected eventual axonal outgrowth, the benefit was less noticeable at days 28 and 35. Immunohistochemistry of the distal axon segments showed an increase number of sensory and motor axons in the NT + PEG group as compared to NT alone. These data suggest that PEG delivery via a conduit may provide a simple, effective way to fuse severed axons and regain early nerve function. For proximal nerve injuries in large animals, recovery of axonal continuity could dramatically improve outcomes, even if fusion only occurs in a small percentage of axons.

Melatonin leads to axonal regeneration, reduction in oxidative stress, and improved functional recovery following sciatic nerve injury.

Despite recent advances in microsurgical techniques and equipments, recovery of function following repair of transected nerves often remains suboptimal. Contrary to traumatic injuries vascular damage that causes peripheral nerve injury has not been well-documented in the literature. In the present study a total of 40 female rats were randomly divided into four groups: Group 1: intact controls (n: 10), Group 2: sham-operated (n: 10), Group 3: vehicle-treated (n: 10), Group 4: melatonin-treated (n: 10). Sciatic nerve damage was created by stripping of the epineurial vessels around the nerve. 50 mg/kg Melatonin was injected intraperitoneally immediately after epineurial stripping in Group 4 in the course of 4 postoperative weeks. We found that melatonin administration after stripping of the epineurial vessels exerted a beneficial effect on axonal regeneration and functional recovery was confirmed by functional (sensory-motor, biochemical, and electrophysiological analyses) and morphological (light microscopic and ultrastructural analyses) data. In the light of these results we concluded that melatonin in a model of sciatic nerve injury leads to axonal regeneration, reducing in oxidative stress, and improved functional recovery.

Regeneration of Axons after Nerve Transection Repair Is Enhanced by Degradation of Chondroitin Sulfate Proteoglycan

Our past work indicates that growth-inhibiting chondroitin sulfate proteoglycan (CSPG) is abundant in the peripheral nerve sheaths and interstitium. In this study we tested if degradation of CSPG by chondroitinase enhances axonal regeneration through the site of injury after (a) nerve crush and (b) nerve transection and coaptation. Adult rats received the same injury bilaterally to the sciatic nerves and then chondroitinase ABC was injected near the injury site on one side, and the contralateral nerve was injected with vehicle alone. Nerves were examined 2 days after injury in the nerve crush model and 4 days after injury in the nerve transection model. Chondroitinase-dependent neoepitope immunolabeling showed that CSPG was thoroughly degraded around the injury site in the chondroitinase-treated nerves. Axonal regeneration through the injury site and into the distal nerve was assessed by GAP-43 immunolabeling. Axonal regeneration after crush injury was similar in chondroitinase-treated and control nerves. In contrast, axonal regrowth through the coaptation of transected nerves was markedly accelerated and the ingress of axons into the distal segment was increased severalfold in nerves injected with chondroitinase. On the basis of these results we concluded that growth inhibition by CSPG contributes critically to the poor regenerative growth of axons in nerve transection repair. In addition, degradation of CSPG by injection of chondroitinase ABC at the site of nerve repair increased the ingress of axonal sprouts into basal laminae of the distal nerve segment, presumably by enabling more latitude in growth at the interface of coapted nerve. This suggests that chondroitinase application may be used clinically to improve the outcome of primary peripheral nerve repair.

Melanocortins in peripheral nerve regeneration: Influence of dosage forms and routes of administration

Neutrophic peptides derived from the melanocortin (ACTH/MSH) family stimulate both in vitro and in vivo the outgrowth of neuntes from developing neurones or damaged nerves. In medical biology the search for a new lead in the pharmacotherapy of brain and nerve lesions is tremendous as the incidence of especially aged related neurodegenerative diseases and nervous system trauma in a greying society is profound and currently little, if any, specific drug treatment seems to be at hand. In rats, the efficacy of melanocortins in accelerating functional recovery from sciatic nerve damage following various types of sub-cutaneous and oral administration was assessed. Rats bearing a crush lesion in the sciatic nerve and receiving melanocortins as a subcutaneous bolus injection every other day showed an accelerated recovery of function as tested in a foot withdrawal test or a walking pattern analysis. Sustained release from osmotic ALZET-minipumps or from lactate/glycolate biodegradable microspheres, both dosage forms implanted subcutaneously, were similarly effective. Although melanocortins have been shown to affect some CNS function following oral administration, both delivery via drinking water and via a stomach tube rendered the peptide ineffective in facilitating peripheral nerve repair. In the study on the pharmacotherapy of nerve trauma, local application of neurotrophic factors is both feasible as well as implicated by pathophysiological mechanisms governing post-lesion neurite outgrowth. In experiments concerning the repair of transected nerves we used microporous Accurel ® polypropylene tubes to enclose the site of injury. The Accurel ® can adsorb high quantities of peptides and this feature was used to deliver α-MSH at the repair site of sutured rat sciatic nerve. In studies on the crushed nerve, local application of the peptide was achieved by wrapping apeptideimpregnated biodegradable gelatine foam matrix (Willospon ®) around the site of injury. Under both conditions local delivery leads to enhanced recovery of function following sciatic nerve damage. That local delivery and not leakage from the local site via systemic routes facilitated the recovery process was evident from control studies where the gelatine foam was wrapped around the contralateral nerve and no facilitated recovery could be established in the ipsilateral crushed nerve. Although currently there is little insight into the actual amount of peptide reaching the site of injury via the different routes of administration, it seems appropriate to conclude that a peak amount of peptide must be available in a short period following the nerve damage to faciliate the repair process. In the clinic different routes may be selected depending upon the nature of the nerve damage, i.e. mechanical trauma (local, biodegradable) or intoxication (bolus injection or biodegradable microspheres).

Progressive ultrastructural changes after peripheral nerve transection and repair

Six rhesus monkeys (Macaca mulatta) underwent sharp transection and repair of the intrinsic motor fascicles of both ulnar nerves in order to determine the sequential events during reinnervation of the distal stamp. Light and electron microscopic sections were made at 2.0 mm increments distal to the neurorrhaphy at weekly intervals in separate monkeys. Neurite sprouts could be identified distal to the neurorrhaphy by 1 week and were clearly evident 40 mm distal by 3 weeks. Although some old endoneurial tubules persisted, they were less often used as conduits or scaffolds for the regenerating neurites than previously described. Most new fibers, whether myelinated or unmyelinated, passed down new endoneurial tubules, thus precluding perfect end-organ specificity because the regenerating neurites seldom utilized old endoneurial tubules. The clinical implication suggested by this study is that the ideal situation is the immediate repair of transected nerves. This allows neurite sprouts to cross a neurorrhaphy rapidly and reinnervate end organs.