Reconstruction of Multiple Facial Nerve Branches Using Skeletal Muscle-Derived Multipotent Stem Cell Sheet-Pellet Transplantation

Head and neck cancer is often diagnosed at advanced stages, and surgical resection with wide margins is generally indicated, despite this treatment being associated with poor postoperative quality of life (QOL). We have previously reported on the therapeutic effects of skeletal muscle-derived multipotent stem cells (Sk-MSCs), which exert reconstitution capacity for muscle-nerve-blood vessel units. Recently, we further developed a 3D patch-transplantation system using Sk-MSC sheet-pellets. The aim of this study is the application of the 3D Sk-MSC transplantation system to the reconstitution of facial complex nerve-vascular networks after severe damage. Mouse experiments were performed for histological analysis and rats were used for functional examinations. The Sk-MSC sheet-pellets were prepared from GFP-Tg mice and SD rats, and were transplanted into the facial resection model (ST). Culture medium was transplanted as a control (NT). In the mouse experiment, facial-nerve-palsy (FNP) scoring was performed weekly during the recovery period, and immunohistochemistry was used for the evaluation of histological recovery after 8 weeks. In rats, contractility of facial muscles was measured via electrical stimulation of facial nerves root, as the marker of total functional recovery at 8 weeks after transplantation. The ST-group showed significantly higher FNP (about three fold) scores when compared to the NT-group after 2–8 weeks. Similarly, significant functional recovery of whisker movement muscles was confirmed in the ST-group at 8 weeks after transplantation. In addition, engrafted GFP⁺ cells formed complex branches of nerve-vascular networks, with differentiation into Schwann cells and perineurial/endoneurial cells, as well as vascular endothelial and smooth muscle cells. Thus, Sk-MSC sheet-pellet transplantation is potentially useful for functional reconstitution therapy of large defects in facial nerve-vascular networks.     

Functional Recovery of Denervated Skeletal Muscle with Sensory or Mixed Nerve Protection: A Pilot Study

Functional recovery is usually poor following peripheral nerve injury when reinnervation is delayed. Early innervation by sensory nerve has been indicated to prevent atrophy of the denervated muscle. It is hypothesized that early protection with sensory axons is adequate to improve functional recovery of skeletal muscle following prolonged denervation of mixed nerve injury. In this study, four groups of rats received surgical denervation of the tibial nerve. The proximal and distal stumps of the tibial nerve were ligated in all animals except for those in the immediate repair group. The experimental groups underwent denervation with nerve protection of peroneal nerve (mixed protection) or sural nerve (sensory protection). The experimental and unprotected groups had a stage II surgery in which the trimmed proximal and distal tibial nerve stumps were sutured together. After 3 months of recovery, electrophysiological, histological and morphometric parameters were assessed. It was detected that the significant muscle atrophy and a good preserved structure of the muscle were observed in the unprotected and protective experimental groups, respectively. Significantly fewer numbers of regenerated myelinated axons were observed in the sensory-protected group. Enhanced recovery in the mixed protection group was indicated by the results of the muscle contraction force tests, regenerated myelinated fiber, and the results of the histological analysis. Our results suggest that early axons protection by mixed nerve may complement sensory axons which are required for promoting functional recovery of the denervated muscle natively innervated by mixed nerve.     

Org.2766 improves functional and electrophysiological aspects of regenerating sciatic nerve in the rat

The beneficial effect of short-term (8 days) melanocortin therapy on regenerating peripheral nerves is demonstrated using functional and electrophysiological tests. Following a crush lesion of the rat sciatic nerve, recovery of sensory function is monitored by assessing the responsiveness of the rat to a small electric current applied to the footsole. Recovery of motor function is assessed by means of an analysis of walking patterns. Normalization of the walking pattern reflects reinnervation of different muscle groups. The motor and H-reflex related sensory nerve conduction velocity of the regenerated nerves are longitudinally investigated in the same rats in which the recovery of motor and sensory function had been assessed previously. Functional tests show an enhanced recovery under melanocortin therapy, but in the end both saline- and melanocortin-treated rats show 100% recovery. However, when compared to the contralateral sciatic nerve, in the peptide-treated animals motor nerve conduction in the regenerated nerves has fully recovered after about 90 days following the crush lesion and the sensory conduction after about 120 days, whereas in the saline-treated rats a deficit of 20-40% in both motor and sensory conduction remains. This difference is observed even 214 days following crush.     

Walking track analysis: a long-term assessment of peripheral nerve recovery.

Functional recovery following sciatic, tibial, and peroneal nerve injury was assessed over a 1-year period using walking track analysis in the rat. Internal neurolysis did not affect nerve function. Crush injury induced a temporary, but complete, loss of function that recovered to control levels by 4 weeks. Nerve transection resulted in complete loss of function without any evidence of recovery. After nerve repair, functional recovery occurred, reaching near-optimal recovery by 12 weeks. The degree of functional recovery varied with the specific nerve involved. The sciatic nerve recovered 41 percent of function, whereas the tibial nerve recovered 54 percent of function. The peroneal nerve exhibited the highest degree of recovery, achieving functional levels similar to control values. Assessment of neural regeneration using walking track analysis appears to be a valuable addition to the traditional methods of histology and electrophysiology.     

Functional evaluation of complete sciatic, peroneal, and posterior tibial nerve lesions in the rat

Quantification of peripheral nerve regeneration in animal studies of nerve injury and repair by histologic, morphologic, and electrophysiologic parameters has been controversial because such studies may not necessarily correlate with actual nerve function. This study modifies the previously described sciatic functional index (SFI), tibial functional index (TFI), and peroneal functional index (PFI) based on multiple linear regression analysis of factors derived from measurements of walking tracks in rats with defined nerve injuries. The factors that contributed to these formulas were print-length factor (PLF), toe-spread factor (TSF), and intermediary toe-spread factor (ITF). It was shown that animals with selective nerve injuries gave walking tracks that were consistent, predictable, and based on known neuromuscular deficits. The new formula for sciatic functional index was compared with previously described indices. The sciatic functional index, tibial functional index, and peroneal functional index offer the peripheral nerve investigator a noninvasive quantitative assessment of hindlimb motor function in the rat with selective hindlimb nerve injury.     

Behavioral evaluation of regenerated rat sciatic nerve by a nanofibrous PHBV conduit filled with Schwann cells as artificial nerve graft

Abstract

The aim of this study is to develop a nanofibrous polymeric nerve conduit with Schwann cells (SCs) and to evaluate its efficiency on the promotion of functional and locomotive activities in rats. The conduits were implanted into a 30-mm gap in the sciatic nerves of the rats. Four months after surgery, the rats were monitored and evaluated by behavioral analyses such as toe out angle, toe spreading analysis, walking track analysis, extensor postural thrust, open-field analysis, swimming test and nociceptive function, four months post surgery. Four months post-operatively, the results from behavioral analyses demonstrated that in the grafted groups especially in the grafted group with SCs, the rat sciatic nerve trunk had been reconstructed with functional recovery such as walking, swimming and recovery of nociceptive function. This study proves the feasibility of artificial conduit with SCs for nerve regeneration by bridging a longer defect in the rat model.     

Functional assessment in the rat by ground reaction forces

Although the rat sciatic nerve model is used extensively in the investigation of repair techniques, and a variety of evaluation methods utilized to assess the results, a means to measure directly and accurately the return of function in these animals is absent. Histologic, histomorphometric, and electrophysiologic methods can be reliable indicators of nerve regeneration but do not correlate to functional recovery. The purposes of this study were to develop apparatus to continuously measure ground reaction forces (GRF) and use GRF parameters in the assessment of gait parameters in normal rats preoperatively and following peripheral nerve severance and repair. Three neurorrhaphy methods: direct sciatic nerve repair, direct tibial nerve repair and double sciatic nerve repair simulating autograft, as well as a non-repaired tibial nerve transection were evaluated. The testing apparatus was designed to measure the spontaneous and voluntary effort of the rat with objective data. Three orthogonal components - vertical, craniocaudal (braking and propulsion), and mediolateral - of the ground reaction force were measured. Preoperative data showed that vertical forces were comparable among the four limbs but propulsion and braking forces displayed significant differences. At 12 weeks, functional recovery was most evident in the direct tibial nerve repair group and absent in the non-repaired tibial defect group. Direct sciatic nerve repairs and sciatic nerve grafts resulted in lesser degrees of improvement. Results indicated that the propulsive force is the optimal GRF parameter for evaluating recovery of useful function.     

Brainstem-evoked muscle potentials: their prognostic value in experimental spinal cord injury in the rat

Recording myoelectric motor-evoked potentials is frequently used as an in vivo evaluation technique in experimental studies of spinal cord injury (SCI). The aim of the present study was to determine whether specific neuronal pathways conduct these potentials. Stainless steel screws were permanently implanted into the cranium of 18 rats for stimulation of brainstem-evoked muscle potentials (B-MPs). Twelve rats were subjected to spinal cord lesions that restricted the continuity of the spinal cord to different discrete sections of the lateral and/or ventral white matter (WM) of the left hemicord. Sham rats (n = 6) were subjected to laminectomy only. Left hind limb B-MPs and motor function (open field walking test) were recorded before surgery and weekly thereafter for six consecutive weeks. Motor function was severely affected by SCI in all rats but recovered significantly during the first 14 postoperative days. The degree of functional recovery depended not only on the amount of spared WM but also on the particular section of WM that had been spared. In contrast, B-MP amplitudes also were severely reduced by SCI, but did not recover during the survival period. Moreover, B-MP amplitudes correlated only weakly with the amount of sparedWM and were not influenced by which section ofWM had been spared. While functional recovery correlated significantly with the amount of spared WM, no correlation was found between B-MP amplitudes and functional recovery. B-MP conduction velocities were not affected by SCI. It is therefore believed that B-MPs have little prognostic value for experimental studies of SCI in the rat.     

Brainstem-evoked muscle potentials: their prognostic value in experimental spinal cord injury in the rat

Recording myoelectric motor-evoked potentials is frequently used as an in vivo evaluation technique in experimental studies of spinal cord injury (SCI). The aim of the present study was to determine whether specific neuronal pathways conduct these potentials. Stainless steel screws were permanently implanted into the cranium of 18 rats for stimulation of brainstemevoked muscle potentials (B-MPs). Twelve rats were subjected to spinal cord lesions that restricted the continuity of the spinal cord to different discrete sections of the lateral and/or ventral white matter (WM) of the left hemicord. Sham rats ( n = 6) were subjected to laminectomy only. Left hind limb B-MPs and motor function (open field walking test) were recorded before surgery and weekly thereafter for six consecutive weeks. Motor function was severely affected by SCI in all rats but recovered significantly during the first 14 postoperative days. The degree of functional recovery depended not only on the amount of spared WM but also on the particular section of WM that had been spared. In contrast, B-MP amplitudes also were severely reduced by SCI, but did not recover during the survival period. Moreover, B-MP amplitudes correlated only weakly with the amount of spared WM and were not influenced by which section of WM had been spared. While functional recovery correlated significantly with the amount of spared WM, no correlation was found between B-MP amplitudes and functional recovery. B-MP conduction velocities were not affected by SCI. It is therefore believed that B-MPs have little prognostic value for experimental studies of SCI in the rat.     

Synergistic Effects of Bone Mesenchymal Stem Cells and Chondroitinase ABC on Nerve Regeneration After Acellular Nerve Allograft in Rats

This study aimed to evaluate whether combination therapy of bone marrow stromal cells (BMSCs) transplantation and chondroitinase ABC (ChABC) treatment further enhances axonal regeneration and functional recovery after acellular nerve allograft repair of the sciatic nerve gap in rats. Eight Sprague–Dawley rats were used as nerve donors, and 32 Wistar rats were randomly divided into four groups: Group I: acellular rat sciatic nerve (ARSN) group; Group II: ChABC treatment; Group III: BMSCs transplantation; and Group IV: ChABC treatment and BMSCs transplantation. The results showed that compared with ARSN control group, BMSC transplantation promoted axonal regeneration, the secretion of neural trophic factors NGF, BDNF and axon angiogenesis in nerve graft. ChABC treatment degraded chondroitin sulfate proteoglycans in ARSN in vitro and in vivo and improved BMSCs survival in ARSN. The combination therapy caused much better beneficial effects evidenced by increasing sciatic function index, nerve conduction velocity, restoration rate of tibialis anterior wet muscle weight, and myelinated nerve number, but did not further boost the therapeutic effects on neurotrophic factor production, axon angiogenesis, and sensory functional recovery by BMSC transplantation. Taken together, for the first time, we demonstrate the synergistic effects of BMSC transplantation and BMSCs treatment on peripheral nerve regeneration, and our findings may help establish novel strategies for cell transplantation therapy for peripheral nerve injury.     

Motor and sensory nerve conduction velocities in Yucatan minipigs

Motor and/or sensory conduction velocities are used to assess peripheral nervous system disorders. Although the miniature pig represents a model of choice for long-term pharmacological experimentation, no study has so far been reported on this model in relation to the measurement of nerve conduction velocities. We developed the present technique and applied it to 34 3-18-month-old Yucatan minipigs. Motor and sensory conduction velocities were measured using the anterior tibial nerve and the internal plantar nerve, a branch of the posterior tibial nerve, respectively. The nerve conduction velocity data of motor (MNCV) and sensory (SNCV) nerves, together with the amplitude of the sensory nerve signal, were logarithmically dependent on the age of the tested animals (r(2)=0.92, 0.81 and 0.76, respectively). The mean values of MNCV and SNCV were 70.9 +/- 1.1 and 67.9 +/- 0.2 m/s, respectively, at the age of 16 months for these miniature pigs. In order to validate this model, we compared it with other known models when the velocities reached a plateau at the end of the study. These values were found to be higher than those in humans or rats, but are comparable to those of the baboon, one of the best large animal models for human pathologies. Because the physiology and metabolism of the minipig resemble those of humans, and due to its long lifetime, this animal represents a good model for studying the development of neuropathology.     

Functional recovery following manipulation of muscles and sense organs in the stick insect leg

We studied functional recovery of leg posture and walking behaviour in the femur-tibia joint control system of stick insects. Leg extensions in resting animals and during walking are produced by different parts of a single extensor muscle. (a) Ablation of the muscle part responsible for fast movements prevented leg extension during the swing phase. Resting posture remained unaffected. Within a few post-operative days, extension movements recovered, provided that sensory feedback was available. Extension movements were now driven by the muscle part which in intact animals controls the resting posture only. (b) Selective ablation of this (slow) muscle part affected the resting posture, while walking was unaffected. The resting posture partly recovered during subsequent days. To test the range of functional recovery and underlying mechanisms, we additionally transected muscle motor innervation, or we inverted or ablated sensory feedback. We found that recovery was based on both muscular and neuronal mechanisms. The latter required appropriate sensory feedback for the process of recovery, but not for the maintenance of the recovered state. Our results thus indicate the existence of a sensory template that guides recovery. Recovery was limited to a behavioural range that occurs naturally in intact animals, though in different behavioural contexts.     

Reduction of skeletal muscle injury in composite tissue allotransplantation by heat stress preconditioning

Ischemia-reperfusion injury is a dominant factor limiting tissue survival in any microsurgical tissue transplantation, a fact that also applies to allogeneic hand transplantation. The clinical experience of the 12 human hand transplantations indicates that shorter ischemia times result in reduced tissue damage and, ultimately, in better hand function. Heat stress preconditioning and the accompanying up-regulation of the heat shock protein 72 have been shown to reduce the ischemia-reperfusion injury following ischemia of various organs, including organ transplantation. The aim of this study was to reduce the ischemia-reperfusion injury in a model of composite tissue allotransplantation. Allogeneic hind limb transplantations were performed from Lewis (donor) to Brown-Norway rats. Donor rats in group A (n = 10) received a prior heat shock whereas rats in group B (n = 10) did not receive any prior heat shock. Group C served as a control group without transplantation. The transplantations were performed 24 hours after the heat shock, at which time the heat shock protein 72 was shown to be up-regulated. The outcome was evaluated 24 hours after transplantation by nitroblue tetrazolium staining and wet-to-dry weight ratio of muscle slices (anterior tibial muscle). The nitroblue tetrazolium staining showed a significant reduction of necrotic muscle in group A (prior heat shock) (p = 0.005). The wet-to-dry ratio was significantly reduced in group A (prior heat shock), indicating less muscle edema and less tissue damage (p = 0.05). Heat shock preconditioning 24 hours before an ischemic event leads to an up-regulation of heat shock protein 72 in muscle and to a tissue protection reducing ischemia-reperfusion injury in composite tissue transplantation.     

Retrograde tracing and toe spreading after experimental autologous nerve transplantation and crush injury of the sciatic nerve: a descriptive methodological study

ABSTRACT: Evaluation of functional and structural recovery after peripheral nerve injury is crucial to determine the therapeutic effect of a nerve repair strategy. In the present study, we examined the relationship between the structural evaluation of regeneration by means of retrograde tracing and the functional evaluation analysis of toe spreading. Two standardized rat sciatic nerve injury models were used to address this relationship. As such, animals received either a 2 cm sciatic nerve defect (neurotmesis) followed by autologous nerve transplantation (ANT animals) or a crush injury with spontaneous recovery (axonotmesis; CI animals). Functional recovery of toe spreading was observed over an observation period of 84 days. In contrast to CI animals, ANT animals did not reach pre-surgical levels of toe spreading. After the observation period, the lipophilic dye DiI was applied to label sensory and motor neurons in dorsal root ganglia (DRG; sensory neurons) and spinal cord (motor neurons), respectively. No statistical difference in motor or sensory neuron counts could be detected between ANT and CI animals. In the present study we could indicate that there was no direct relationship between functional recovery (toe spreading) measured by SSI and the number of labelled (motor and sensory) neurons evaluated by retrograde tracing. The present findings demonstrate that a multimodal approach with a variety of independent evaluation tools is essential to understand and estimate the therapeutic benefit of a nerve repair strategy.     

Transplantation of miR-219 overexpressed human endometrial stem cells encapsulated in fibrin hydrogel in spinal cord injury

Oligodendrocyte (OL) loss and demyelination occur after spinal cord injury (SCI). Stimulation of remyelination through transplantation of myelinating cells may be effective in improving function. For the repair strategy to be successful, the selection of a suitable cell and maintaining cell growth when cells are injected directly to the site of injury is important. In addition to selecting the type of cell, fibrin hydrogel was used as a suitable tissue engineering scaffold for this purpose. To test the relationship between myelination and functional improvement, the human endometrial stem cells (hEnSCs) were differentiated toward oligodendrocyte progenitor cells (OPCs) using overexpression of miR-219. Adult female Wistar rats were used to induce SCI by using a compression model and were randomly assigned to the following four experimental groups: SCI, Vehicle, hEnSC, and OPC. Ten days after injury, miR-219 overexpressed hEnSC-derived OPCs encapsulated in fibrin hydrogel, as an injectable scaffold, were injected to the injury site. In this study, with a focus on promoting functional recovery after SCI, the Basso-Beattie-Bresnahan test was performed to evaluate the recovery of motor function every week for 10 weeks and the histological assay was then performed. Results showed that the rate of motor function recovery was significantly higher in OPC group compared to SCI and vehicle groups but no marked differences were found between OPC and hEnSC groups, although, the rate of myelination in the OPC group was significantly higher than the other groups. These results demonstrated that remyelination was not the cause of recovery of motor function.     

Transplantation of bone marrow-derived mononuclear cells improves mechanical hyperalgesia, cold allodynia and nerve function in diabetic neuropathy

Relief from painful diabetic neuropathy is an important clinical issue. We have previously shown that the transplantation of cultured endothelial progenitor cells or mesenchymal stem cells ameliorated diabetic neuropathy in rats. In this study, we investigated whether transplantation of freshly isolated bone marrow-derived mononuclear cells (BM-MNCs) alleviates neuropathic pain in the early stage of streptozotocin-induced diabetic rats. Two weeks after STZ injection, BM-MNCs or vehicle saline were injected into the unilateral hind limb muscles. Mechanical hyperalgesia and cold allodynia in SD rats were measured as the number of foot withdrawals to von Frey hair stimulation and acetone application, respectively. Two weeks after the BM-MNC transplantation, sciatic motor nerve conduction velocity (MNCV), sensory nerve conduction velocity (SNCV), sciatic nerve blood flow (SNBF), mRNA expressions and histology were assessed. The BM-MNC transplantation significantly ameliorated mechanical hyperalgesia and cold allodynia in the BM-MNC-injected side. Furthermore, the slowed MNCV/SNCV and decreased SNBF in diabetic rats were improved in the BM-MNC-injected side. BM-MNC transplantation improved the decreased mRNA expression of NT-3 and number of microvessels in the hind limb muscles. There was no distinct effect of BM-MNC transplantation on the intraepidermal nerve fiber density. These results suggest that autologous transplantation of BM-MNCs could be a novel strategy for the treatment of painful diabetic neuropathy.     

Flexible multibody simulation approach in the analysis of tibial strain during walking

Strains within the bone tissue play a major role in bone (re)modeling. These small strains can be assessed using experimental strain gage measurements, which are challenging and invasive. Further, the strain measurements are, in practise, limited to certain regions of superficial bones only, such as the anterior surface of the tibia. In this study, tibial strains occurring during walking were estimated using a numerical approach based on flexible multibody dynamics. In the introduced approach, a lower body musculoskeletal model was developed by employing motion capture data obtained from walking at a constant velocity. The motion capture data were used in inverse dynamics simulation to teach the muscles in the model to replicate the motion in forward dynamics simulation. The maximum and minimum tibial principal strains predicted by the model were 490 and -588 microstrain, respectively, which are in line with literature values from in vivo measurements. In conclusion, the non-invasive flexible multibody simulation approach may be used as a surrogate for experimental bone strain measurements and thus be of use in detailed strain estimations of bones in different applications.     

Cutaneous Collateral Axonal Sprouting Re-Innervates the Skin Component and Restores Sensation of Denervated Swine Osteomyocutaneous Alloflaps

Reconstructive transplantation such as extremity and face transplantation is a viable treatment option for select patients with devastating tissue loss. Sensorimotor recovery is a critical determinant of overall success of such transplants. Although motor function recovery has been extensively studied, mechanisms of sensory re-innervation are not well established. Recent clinical reports of face transplants confirm progressive sensory improvement even in cases where optimal repair of sensory nerves was not achieved. Two forms of sensory nerve regeneration are known. In regenerative sprouting, axonal outgrowth occurs from the transected nerve stump while in collateral sprouting, reinnervation of denervated tissue occurs through growth of uninjured axons into the denervated tissue. The latter mechanism may be more important in settings where transected sensory nerves cannot be re-apposed. In this study, denervated osteomyocutaneous alloflaps (hind- limb transplants) from Major Histocompatibility Complex (MHC)-defined MGH miniature swine were performed to specifically evaluate collateral axonal sprouting for cutaneous sensory re-innervation. The skin component of the flap was externalized and serial skin sections extending from native skin to the grafted flap were biopsied. In order to visualize regenerating axonal structures in the dermis and epidermis, 50um frozen sections were immunostained against axonal and Schwann cell markers. In all alloflaps, collateral axonal sprouts from adjacent recipient skin extended into the denervated skin component along the dermal-epidermal junction from the periphery towards the center. On day 100 post-transplant, regenerating sprouts reached 0.5 cm into the flap centripetally. Eight months following transplant, epidermal fibers were visualized 1.5 cm from the margin (rate of regeneration 0.06 mm per day). All animals had pinprick sensation in the periphery of the transplanted skin within 3 months post-transplant. Restoration of sensory input through collateral axonal sprouting can revive interaction with the environment; restore defense mechanisms and aid in cortical re-integration of vascularized composite allografts.     

The effects of cisplatinum and vincristine on peripheral nerve regeneration

Current treatment modalities for extremity sarcoma often include tumor extirpation plus neoadjuvant therapy. Limb-sparing surgery may require reconstruction of critical nerve defects. Neurotoxic side effects from adjuvant chemotherapy have been reported and raise concerns regarding the effects of chemotherapy on nerve regeneration. In an attempt to define the effects of adjuvant chemotherapy on peripheral nerve regeneration, cisplatin and vincristine were administered to rats following isografting of the posterior tibial nerve. Parameters used to assess peripheral nerve regeneration included walking track analysis and histomorphology. Sixty 250-g Sprague-Dawley rats were randomly allocated into one of three treatment groups. Each animal underwent a 15-mm reversed interposition nerve isograft from 30 donor rats into the right posterior tibial nerve. Ten animals served as control. The remaining animals were divided into two groups of 25 animals each. One group received cisplatin (75 mg/m2) and the other group received vincristine (1 mg/m2). Chemotherapy was administered at 4-week cycles for a total of six cycles (24 weeks). Walking track analysis was performed monthly. Nerve specimens were harvested from the grafted segment and the distal posterior tibial nerve for histomorphology. Walking track analysis demonstrated no statistical difference in print length between the control and chemotherapeutic groups at the conclusion of the study. The number of axons per square millimeter and nerve fiber density were not statistically different between control and chemotherapeutic groups. In the rodent posterior tibial nerve model, postoperative adjuvant therapy does not significantly alter functional outcome in peripheral nerve regeneration. The practice of immediate nerve grafting after tumor extirpation, despite planned postoperative chemotherapy, is supported.     

Book Review

Mechanosensory activity was recorded extracellularly from branches of the internal pedal nerve in the femur of the horseshoe crab walking leg. The receptors appeared to be associated with the tibial flexor muscles and generally showed little spontaneous activity in the isolated leg. Sensory activity was most easily and reliably elicited by active flexor contraction against a load, and it did not require joint movement. The neurons responsible for this activity appear to be true series tension receptors. Since such cells are likely to be adequately stimulated only by tension developed in muscle fibers with which they are in series, whole muscle tension is not always directly related to the activity of a given receptor. In order to estimate the magnitude of the force at a receptor under study various indirect methods of altering the tension in and spatial relationships between the fibres of a single muscle were employed. These include active stimulation while (a) fixing the muscle at various lengths (joint angles), (b) lengthening or shortening the muscle passively over a wide range and at varying rates. The results obtained are consistent with the suggestion that the sensory cells are series tension receptors.