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Background:  Nerve transfers from one common donor nerve to recipient nerves with multiple target branches can yield slower and unpredictable recovery in the target nerves. Our hypothesis is that steal phenomenon exists when multiple nerve neurotization comes from one donor nerve., Methods:  In 30 Sprague-Dawley rats, the left ulnar nerve (UN) was selected as the donor nerve, and the musculocutaneous nerve (MCN) and median nerve (MN) as the recipient target nerves. The rats were separated into three groups (10 rats in each): group A, UN-to-MCN (one-target); group B, UN-to-MN (one-target); and group C, UN-to-MCN and MN (two-target). The right upper limbs were nonoperative as the control group. Outcome obtained at 20 weeks after surgery included grooming test, muscle weight, compound muscle action potential, tetanic muscle contraction force, axon counts, and retrograde labeling of the involved donor and target nerves., Results:  At 20 weeks after surgery, muscles innervated by neurotization resulted in significant worse outcomes than the control side. This was especially true in two-target neurotization in the parameter of muscle weight and forearm flexor muscle contraction force outcome when compared to one-target neurotization. Steal phenomenon does exist because flexor muscle contraction force was significantly worse during two-target neurotization., Conclusion:  This study proves the existence of steal phenomenon in multiple target neurotization but does not significantly affect the functional results. Postoperative rehabilitative measures (including electrical stimulation, induction exercise) and patient compliance (ambition and persistence) are other crucial factors that hold equivalent importance to long-term successful recovery., Competing Interests: None declared., (Thieme. All rights reserved.)

Background: Traumatic peripheral nerve injury, with an annual incidence reported to be approximately 13-23 per 100,000 people, is a serious clinical condition that can often lead to significant functional impairment and permanent disability. Although nerve transfer has become increasingly popular in the treatment of brachial plexus injuries, satisfactory results cannot be obtained even with total nerve root transfer, especially after serious injuries. To overcome this problem, we hypothesize that the application of stem cells in conjunction with nerve transfer procedures may be a viable alternative to more aggressive treatments that do not result in adequate improvement. Similarly, some preliminary studies have shown that adipose stem cells combined with acellular nerve allograft provide promising results in the repair of brachial plexus injury. The purpose of this study was to assess the efficacy of combining adipose-derived stem cells with nerve transfer procedure in a rat brachial plexus injury model., Methods: Twenty female Wistar rats weighing 300-350 g and aged 8-10 weeks were randomly divided into two groups: a nerve transfer group (NT group) and a nerve transfer combined adipose stem cell group (NT and ASC group). The upper brachial plexus injury model was established by gently avulsing the C5-C6 roots from the spinal cord with microforceps. A nerve transfer from the ulnar nerve to the musculocutaneous nerve (Oberlin procedure) was performed with or without seeded allogeneic adipose tissue-derived stem cells. Adipose tissue-derived stem cells at a rate of 2 × 10 6  cells were injected locally to the surface of the nerve transfer area with a 23-gauge needle. Immunohistochemistry (S100 and PGP 9.5 antibodies) and electrophysiological data were used to evaluate the effect of nerve repair 12 weeks after surgery., Results: The mean latency was significantly longer in the NT group (2.0 ± 0.0 ms, 95% CI: 1.96-2.06) than in the NT and ASC group (1.7 ± 0.0 ms, 95% CI: 1.7-1.7) (p < .001). The mean peak value was higher in the NT group (1.7 ± 0.0 mV, 95% CI: 1.7-1.7) than in the NT and ASC group (1.7 ± 0.3 mV, 95% CI: 1.6-1.9) with no significant difference (p = .61). Although S100 and PGP 9.5 positive areas were observed in higher amounts in the NT and ASC group compared to the NT group, the differences were not statistically significant (p = .26 and .08, respectively)., Conclusions: This study conducted on rats provides preliminary evidence that adipose-derived stem cells may have a positive effect on nerve transfer for the treatment of brachial plexus injury. Further studies with larger sample sizes and longer follow-up periods are needed to confirm these findings., (© 2024 Wiley Periodicals LLC.)

Functional recovery following peripheral nerve injury worsens with increasing durations of delay prior to repair. From the time of injury until re-innervation occurs, denervated muscle undergoes progressive atrophy that limits the extent to which motor function can be restored. Similarly, Schwann cells (SC) in the distal nerve lacking axonal interaction progressively lose their capacity to proliferate and support regenerating axons. The relative contributions of these processes to diminished functional recovery is unclear. We developed a novel rat model to isolate the effects of SC vs. muscle denervation on functional recovery. Four different groups underwent the following interventions for 12 weeks prior to nerve transfer: 1) muscle denervation; 2) SC denervation; 3) muscle + SC denervation (negative control); 4) no denervation (positive control). Functional recovery was measured weekly using the stimulated grip strength testing (SGST). Animals were sacrificed 13 weeks post nerve transfer. Retrograde labeling was used to assess the number of motor neurons that regenerated their axons. Immunofluorescence was performed to evaluate target muscle re-innervation and atrophy, and to assess the phenotype of the SC within the distal nerve segment. Functional recovery in the muscle denervation and SC denervation groups mirrored that of the negative and positive control groups, respectively. The SC denervation group achieved better functional recovery, with a greater number of reinnervated motor endplates and less muscle atrophy, than the muscle denervation group. Retrograde labeling suggested a higher number of neurons contributing to muscle reinnervation in the muscle denervation group as compared to SC denervation (p > 0.05). The distal nerve segment in the muscle denervation group had a greater proportion of SCs expressing the proliferation marker Ki67 as compared to the SC denervation group (p < 0.05). Conversely, the SC denervation group had a higher percentage of senescent SCs expressing p16 as compared to the muscle denervation group (p < 0.05). The deleterious effects of muscle denervation are more consequential than the effects of SC denervation on functional recovery. The effects of 12 weeks of SC denervation on functional outcome were negligible. Future studies are needed to determine whether longer periods of SC denervation negatively impact functional recovery., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Peripheral nerve gaps often lead to interrupted innervation, manifesting as severe sensory and motor dysfunctions. The repairs of the nerve injuries have not achieved satisfactory curative effects in clinic. The transplantation of bone marrow stromal cells (BMSCs)-laden acellular nerve xenografts (ANX) has been proven more effective than the acellular nerve allografting. Besides, granulocyte colony-stimulating factor (G-CSF) can inhibit inflammation and apoptosis, and thus is conducive to the microenvironmental improvement of axonal regeneration. This study aims to investigate the joint effect of BMSCs-seeded ANX grafting and G-CSF administration, and explore the relevant mechanisms. Adult SD rats were divided into five groups randomly: ANX group, ANX combined with G-CSF group, BMSCs-laden ANX group, BMSCs-laden ANX combined with G-CSF group, and autograft group. Eight weeks after transplantation, the detection of praxiology and neuroelectrophysiology was conducted, and then the morphology of the regenerated nerves was analyzed. The inflammatory response and apoptosis in the nerve grafts as well as the expression of the growth-promoting factors in the regenerated tissues were further assayed. G-CSF intervention and BMSCs implanting synergistically promoted peripheral nerve regeneration and functional recovery following ANX bridging, and the restoration effect was matchable with that of the autologous nerve grafting. Moreover, local inflammation was alleviated, the apoptosis of the seeded BMSCs was decreased, and the levels of the neuromodulatory factors were elevated. In conclusion, the union application of BMSCs-implanted ANX and G-CSF ameliorated the niche of neurotization and advanced nerve regeneration substantially. The strategy achieved the favorable effectiveness as an alternative to the autotransplantation., (© 2019 Wiley Periodicals, Inc.)

Background: In infant poliomyelitis or poliomyelitis-like paresis, there has been no means of treating residual paralysis and the policy has been to wait until an affected infant has grown sufficiently to enable tendon transfer or arthrodesis. However, recent reports have described relatively good results for early surgical intervention in the form of nerve transfer., Methods: In a 4-year and 6-month-old child we transferred a partial ulnar nerve for elbow flexor reconstruction even 3 years and 10 months after the onset of poliomyelitis-like palsy and also transferred partial accessory and radial nerves for shoulder function restoration 6 months after the first operation., Results: Elbow flexor restored M4 on the British Medical Research Council scale. The shoulder subluxation resolved, however, the strengths of the deltoid and infraspinatus remained almost M1. At the most recent clinical examination, the patient was 18 years old and the active range of motion of patient's left elbow was 0°-125°, and those of the whole shoulder girdle were abduction 35°, flexion 60°, extension 30° and external rotation 0°., Conclusions: The outcomes we achieved may support partial nerve transfer techniques as viable treatment options for persistent long-standing motor deficits following poliomyelitis-like palsy in children. However, we recommend performing partial nerve transfer as early as possible after recovery from flaccid paralysis and also use of nerves that derive from narrow spinal cord segments. After denervation, children's neuromuscular systems seem to have the ability to regenerate after a much longer period than has generally been believed. This speculation is based on only a single case report; thus, more experience is needed before this generalization can confidently be made., (Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Distal nerve transfer has proven efficacy. The purpose of this study was to investigate if an injured nerve can be used as a donor nerve for transfer, and to determine the threshold of injury., Materials and Methods: Rat's left ulnar-nerves in the axilla with different degrees of injury were selected as the donor nerves for transfer, and the musculocutaneous-nerves the target nerves for being re-innervated. Six rats each served as positive and negative controls: Group A, intact ulnar-nerve transfer; and Group E, the ulnar-nerve was cut but no transfer. Ten rats each were assigned to Group B to Group D with 25%, 50%, and 75% transected ulnar-nerve, respectively and all were transferred to the musculocutaneous-nerve. After a 12-week recovery period, outcomes were evaluated., Results: Biceps muscle weight measurements showed all experimental groups-D 0.28 ± 0.02 g/72%, C 0.28 ± 0.03 g/73%, B 0.29 ± 0.04 g/74%, and A 0.29 ± 0.04 g/80%-were lighter than group H 0.36 ± 0.04 g, which were all statistically significant (P < 0.001). Muscle tetanus contraction force measurements were the lowest in group D35 ± 8.6 g/69%. Groups C and B measured 41 ± 8.5 g/75% and 40 ± 2.2 g/77% and group A 41 ± 9.4 g/95%, respectively. Group H showed muscle contraction force of 52 ± 7.2 g, which was statistically significant when compared to experimental groups (P < 0.05-0.001). EMG measurements of the biceps muscles showed: group D was 3.6 ± 0.7 mV/69%, group C was 3.6 ± 0.6 mV/75%, and group B was 4.2 mV ± 0.7/81%. Group H was5.1 ± 0.7 mV and statistically significant different when compared with experimental groups (P < 0.05-0.001).Axon counts of healthy ulnar-nerve (Group H) were 1849 ± 362. Axon counts of the injured ulnar-nerve were in group B 1447 ± 579/78%, group C 1051 ± 367/57% and group D 567 ± 230/31%., Conclusion: The donor nerve should be healthy in order to provide optimal result. A big nerve (e.g., ulnar nerve) but injured with at least 75% axon spared is still potentially effective for transfer. In contrast, a small nerve (e.g., intercostal nerve) once injured with 75%axon spared would be considered a suboptimal donor nerve., (© 2017 Wiley Periodicals, Inc.)

Peripheral nerve defects result in severe denervation presenting sensory and motor functional incapacitation. Currently, a satisfactory therapeutic treatment promoting the repair of injured nerves is not available. As shown in our previous study, acellular nerve xenografts (ANX) implanted with bone marrow stromal cells (BMSCs) replaced allografts and promoted nerve regeneration. Additionally, granulocyte-colony stimulating factor (G-CSF) has been proven to mobilize supplemental cells and enhance vascularization in the niche. Thus, the study aimed to explore whether the combination of G-CSF and BMSC-laden ANX exhibited a synergistic effect. Adult Sprague-Dawley (SD) rats were randomly divided into five groups: ANX group, ANX combined with G-CSF group, BMSCs-laden ANX group, BMSCs-laden ANX combined with G-CSF group and autograft group. Electrophysiological parameters and weight ratios of tibialis anterior muscles were detected at 8 weeks post-transplantation. The morphology of the regenerated nerves was assayed, and growth-promoting factors present in the nerve grafts following G-CSF administration or BMSCs seeding were also investigated. Nerve regeneration and functional rehabilitation induced by the combination therapy were significantly advanced, and the rehabilitation efficacy was comparable with autografting. Moreover, the expression of Schwann cell markers, neurotrophic factors and neovessel markers in the nerve grafts was substantially increased. In conclusion, G-CSF administration and BMSCs transplantation synergistically promoted the regeneration of ANX-bridged nerves, which offers a superior strategy to replace autografts in repairing peripheral nerve injuries., (© 2017 Wiley Periodicals, Inc.)

Background: Current surgical management of obstetrical brachial plexus injury is primary reconstruction with sural nerve grafts. Recently, the nerve-to-nerve transfer technique has been used to treat brachial plexus injury in adults, affording the benefit of distal coaptations that minimize regenerative distance. The purpose of this study was to test the hypothesis that nerve transfers are effective in reconstructing isolated upper trunk obstetrical brachial plexus injuries., Methods: Ten patients aged 10 to 18 months were treated with three nerve transfers: spinal accessory nerve to the suprascapular nerve for shoulder abduction and external rotation; a radial to axillary nerve for shoulder abduction; and ulnar or median nerve transfer to the musculocutaneous nerve for elbow flexion. Patients were assessed preoperatively and postoperatively using the Active Movement Scale. All patients were followed regularly for up to 2 years., Results: Improvement in elbow and shoulder function was observed between 6 and 24 months. By 6 months, all patients passed the cookie test. At 24 months, shoulder abduction improved from 3.7 ± 0.6 to 5.0 ± 0.5, shoulder external rotation from 1.8 ± 0.4 to 4.3 ± 0.6, shoulder flexion from 3.7 ± 0.5 to 5.4 ± 0.5, elbow flexion from 3.7 ± 0.6 to 6.3 ± 0.2, and forearm supination from 2.1 ± 0.4 to 5.9 ± 0.2. There was no clinically appreciable donor-site morbidity., Conclusions: Nerve transfers reduced operative times compared with traditional nerve grafting procedures. Those patients showed significant gains in Active Movement Scale score by 24 months postoperatively, comparable to results achieved by nerve grafting. These findings support nerve transfers as a potential alternative treatment option for upper trunk obstetrical brachial plexus injuries., Clinical Question/level of Evidence: Therapeutic, IV.

Using ulnar nerve as donor and musculocutaneous nerve as recipient we recently demonstrated that end-to-end neurorrhaphy in young adult male Wistar rats resulted in good recovery following protracted survival. Here we explored whether anti-inflammatory drug- methylprednisolone, regeneration/myelination-enhancing agent- methylcobalamin and neurite growth-enhancing and angiogenic factor- pleiotrophin accelerated its recovery. Methylprednisolone suppressed the perineuronal microglial reaction and periaxonal ED-1 expression while pleiotrophin increased the blood vessel density and nerve fiber densities in the reconnected nerve as expected. Neither methylprednisolone nor methylcobalamin altered the expression of growth associated protein 43 in the neurons examined suggesting that they did not interfere with axonal regeneration attempt. Surprisingly methylcobalamin enhanced the recovery of compound muscle action potentials and motor end plate innervation and the performance on sticker removal grooming test and augmented the diameters and myelin thicknesses of regenerated axons dramatically while enhancing S-100 expression in Schwann cells; remarkable recovery was achieved 1 month following neurorrhaphy. Simultaneous methylcobalamin and pleiotrophin treatment resulted in quick and persistent supernumerary reinnervation but failed to enhance the recovery over that of the former alone. Methylprednisolone transiently suppressed the enumeration of regrowing axons. In conclusion, methylcobalamin may be preferred over methylprednisolone to facilitate the recovery of peripheral nerves following end-to-end neurorrhaphy. The long-term effect of this treatment however remains to be clarified., (Copyright © 2010 IBRO. Published by Elsevier Ltd. All rights reserved.)

Background: The Rho family of small GTPases is responsible for various processes involving actin cytoskeleton in eukaryotic cells, including neurite outgrowth. Several substances found at the peripheral nerve injury site were shown to activate one member of this family, Rho. The activation of Rho leads to neurite outgrowth inhibition and the development of posttraumatic neuropathic pain. The authors used the clinically tested Rho-associated kinase inhibitor fasudil hydrochloride to enhance the functional recovery of the peripheral nerve in the rat., Methods: In the peroneal nerve interpositional graft model, the authors administered fasudil (experimental groups) or saline (control groups) (1) intraperitoneally and (2) directly into the graft by microinjection (n = 6 animals per experimental condition). Neural recovery was assessed during postoperative follow-up lasting 80 days by peroneal functional index, electrophysiologic, and histomorphometric analyses., Results: The peroneal functional index returned to values not significantly different from preoperative values on days 55 (fasudil injected into the graft) and 60 (fasudil injected intraperitoneally) in the experimental groups. In the control groups, this took 70 (saline injected intraperitoneally) and 75 days (saline injected into the graft). These results are supported by electrophysiologic and histomorphologic assessments., Conclusions: The authors determined that fasudil hydrochloride was capable of accelerating the functional regeneration after peripheral nerve axotomy, which is consistent with the results of reports about Rho cascade disruption in the central nervous system. Because fasudil hydrochloride is a clinically tested drug, it could be used to enhance neural regeneration in human patients as well.

Purpose: Recently we successfully used a conduit of epsilon-caprolactone-co-trimethylene carbonate filled with Schwann cells (SC) across a 20 mm gap in a rat median nerve. In this study we applied the tubes with SC across a 40 mm gap in order to analyse the regenerative potential of the tubes in long nerve defects., Methods: To augment the nerve defect a cross-chest procedure was used and the tubes were implanted with injected isogeneic SCs inside (group 3). Both ulnar nerves were used for a 40 mm autograft (group 2). For control group non-operated animals were used (group 1). The grasping test, histology (S-100, PAM), electrophysiology, and the muscle weight were used to assess regeneration., Results: After 12 months, grasping was seen only in three animals of group 3 (3.6 g [95% CI: 0 to 7.6 g]). However, in group 2 all rats had a partial functional regeneration (42.8 g [95% CI: 39.1 to 46.6 g]). The grasping force of the non-operated animals (group 1) was 240.9 g [95% CI: 237.2 to 244.7 g] at the time. Histology from group 3 confirmed an irregular arrangement of fibres in contrast to more organized structures in group 2. Electrophysiology in group 3 displayed potentials only in the three animals with functional regeneration. In group 2 all animals exhibited potentials. A significant decrease of muscle weight was observed in groups 2 and 3, most prominent in the latter., Conclusion: Regeneration was not successful across the 40 mm gap using the applied tube in combination with SC. For future experiments further consideration should be taken in optimizing the cellular and material components that are critical for a successful application to overcome very large nerve gaps.

A new animal model for the study of nerve regeneration in rats across a 40 mm gap between both median nerves is described. For autologous grafting, the ulnar nerves were dissected and sutured together. From the left median nerve, they were transplanted across the chest to the right median nerve. Animals having undergone this operation were observed for 12 months and periodically assessed using the grasping test and measurements of body-weight. For histological analysis rats were sacrificed after this period and axon counts were determined at the suture points of operated animals and in the median nerve of non-operated animals. Functional recovery could be seen, although partially, beginning as early as the fifth postoperative month, as demonstrated by the grasping test. Quantification of the number of axons demonstrated axonal regeneration across all three coaptation points. This model provides a new approach for analysis of long distance peripheral nerve regeneration without impairment of behaviour.

Nerve allotransplantation has been used successfully in human subjects to restore function after traumatic nerve injury and avoid subsequent limb amputation. However, due to the morbidity associated with nonspecific immunosuppression, this reconstructive approach has been limited to patients with particularly severe nerve injuries. It would be desirable to broaden the indications for such procedures through development of less toxic antirejection therapies. A miniature swine model of nerve transplantation was used to investigate the effects of preoperative ultraviolet-B (UV-B)-irradiated donor alloantigen portal venous infusion and injection of cultured major histocompatibility complex (MHC)-matched Schwann cells into the nerve graft. The transplanted ulnar nerves were harvested at 20 weeks. Histomorphometry showed marked enhancement in nerve regeneration through allografts injected with Schwann cells. Serial mixed lymphocyte assays demonstrated suppression of the recipient immune response to the donor antigen after pretreatment, but no additional neuroregenerative effect of donor alloantigen pretreatment.

Background: In brachial plexus injury, elbow flexion is the first priority in reconstruction. Neglected cases need functioning free muscle transplantation that requires the donor nerve to supply the transplanted muscle. The purpose of this study was to investigate the effects and results of transferring one fascicle of the ulnar nerve to the transplanted gracilis muscle., Methods: One woman and two men with neglected avulsions of the C5,C6 roots of the brachial plexus underwent free gracilis muscle transfer for elbow flexion. One fascicle of the ulnar nerve was used as the donor nerve., Results: The mean period of follow-up was 33.3 months. The average reinnervation time of gracilis muscle was 3.7 months. At the final examination, the mean strength of elbow flexion was 4.3 kgf. The grip strength, moving two-point discrimination and the strength of the wrist volar flexion on the affected side was not worse than before surgery in any patient at the last follow-up examination., Conclusions: A fascicle of the ulnar nerve can be one of the most effective options for functioning free muscle transplantation for elbow flexion.

We investigated regeneration across a long nerve defect in the swine model to study extensive neural loss and long nerve gap. Most experiments have been conducted in the rodent model that, while an appropriate immunological model, only allows short nerve gaps to be studied. Twelve outbred swine received either an 8-cm ulnar nerve autograft or an allograft without immunosuppression. At 6 and 10 months, histomorphometry of the autografts demonstrated excellent nerve regeneration, while very poor regeneration was noted across the allografts. This confirmed that 8 cm are an adequate challenge independent of the spontaneous regeneration potential of axons seen in rodents. The swine ulnar nerve graft model causes minimal morbidity and will now be used with immunological manipulation of inbred animals.

The repair of large peripheral nerve defects is not always possible, especially when the proximal stump is not available. In these cases, end-to-side nerve anastomosis has been proposed. In the present experiment, using the terminal branches of the rat brachial plexus, the authors studied behavioral responses after end-to-side nerve anastomoses using fibrin glue, 3 and 6 months after surgery. Rats were evaluated by results of a grasping test, a capsaicin test and a hot-plate test. The collected data demonstrated that there was no functional motor or sensory reinnervation after the end-to-side nerve anastomoses. The conjunctive layers of the peripheral nerve thus represented an effective barrier to reinnervation.

Despite the introduction of microsurgical techniques into clinical practice, the results of surgical procedures involving the brachial plexus and peripheral nerves are still far from spectacular. We therefore studied the rat brachial plexus and its terminal branches in 203 rats. Detailed anatomic and morphologic analyses of the biceps brachii and musculocutaneous nerve, finger flexors, flexor carpi radialis, and the median nerve were performed. Various sources of conventional and vascularized nerve grafts were explored. After musculocutaneous nerve section or median nerve section, there were no articular contractures or automutilations, which constitutes an advantage for these experimental models over the sciatic nerve model. The brachial plexus and its terminal branches provide a good experimental model which can be used to assess the development and normal control of muscle function, examine the mechanisms underlying functional recovery, and test the effects of treatments to enhance recovery.

With the use of ulnar nerves of cynomolgus monkeys, the present study examined whether basal laminae of Schwann cells can serve as conduits for regenerating axons in nerve allografts from non-human primates. A segment of ulnar nerve was transected distal to the elbow joint one week before grafting. In Group A, a distal segment of the transected nerve was transplanted, after freezing and thawing, into the ulnar nerve of another monkey, at a level that corresponded to that from which the graft was taken. In Group B (the control group), the segment of nerve was grafted in the same manner but without cryotreatment. Two weeks, five weeks, eight weeks, and five months after grafting, the graft and the host nerve were examined with light and electron microscopy. Within two weeks after grafting in Group A, after degradation of the cellular components of the Schwann cells, the basal laminae of the Schwann cells were intact in the form of tubes. Within five weeks, many regenerating axons grew out into these basal lamina tubes in the three-centimeter-long grafts and extended into the host nerve. As seen at the wrist (seven centimeters from the distal suture) five months after grafting, the axons exhibited fully mature myelination both in the graft and in the host nerve. In contrast, in Group B, in which the Schwann cells had not been disrupted by cryotreatment, cellular components and connective-tissue matrices, including basal laminae, had been degraded and had been replaced by invading cells, which filled the endoneurial spaces of the graft. Five months after grafting, axonal growth had been arrested in the graft one centimeter distal to the proximal suture. The beneficial effect in Group A appears to have been the result of the retention and preservation of intact basal laminae of Schwann cells after rapid removal of killed Schwann cells and myelin debris. Killing of Schwann cells by freezing before grafting may abolish the immune response to the Schwann cells in allografts and lead to fragmentation and disruption of myelin, which facilitates the rapid removal of myelin by macrophages.