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Peripheral nerve regeneration using acellular nerve grafts.

Long gap peripheral nerve injuries usually require a graft to facilitate axonal regeneration into the distal nerve stump. The use of autografts is often limited because of graft availability and donor-site morbidity. We investigated whether acellular nerve allografts would provide an appropriate channel for the promotion and induction of sciatic nerve regeneration in rats. Axons sprouted from the proximal portion and reached the distal portion in the 1 cm-long grafts by 1 month. The number of axons in the regenerated nerves was similar to that of normal nerves at 1 month. Loading the grafts with betaNGF and VEGF increased the number and mean diameter of axons and neovascularization in the regenerated nerves at 1 month. The motor conduction velocity increased over time and reached 63 +/- 10% of that of normal nerves at 6 months. The nerve injuries treated with the acellular grafts had a significant improvement in motor, nociception, and proprioception function compared to untreated nerves. The results from this study suggest that acellular nerve allografts may be a useful biomaterial for functional peripheral nerve regeneration.

Animals↗

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.

Animals↗

Regeneration of perivascular adrenergic innervation in rat tibial nerve after nerve crush.

Adrenergic innervation of blood vessels in the rat tibial nerve during degeneration and regeneration was studied using the formaldehyde-induced fluorescence method. The left sciatic nerve was crushed with suture threads to produce a 4-mm length of crushed nerve. At 1, 3, 7, 14, 28, 56 and 84 days after nerve crush, degenerative and regenerative changes in the nerve were verified using light microscopy. At each time point, adrenergic innervation was examined in epi-perineurial whole mount and nerve cross-section preparations. One day after nerve crush, fluorescence of adrenergic nerve fibers in the endoneurium was absent. Fluorescent adrenergic nerve fibers reappeared in the endoneurium at day 56 and reached the control density by 84 days. In the epi-perineurium, adrenergic innervation of small and medium-size arterioles was absent at 3 days, in large arterioles at 7 days. At 56 days, all epi-perineurial arterioles were reinnervated by a faint, sparse adrenergic network, which reached the control density at 84 days. The results suggest that adrenergic innervation in the rat peripheral nerve is lost during nerve degeneration, but recovers when the nerve has regenerated.

Animals↗

The effects of delayed nerve repair on neuronal survival and axonal regeneration after seventh cervical spinal nerve axotomy in adult rats.

It has been proposed clinically that delayed surgery after traumatic brachial plexus injury may adversely affect functional outcome. In the present experimental study the neuroprotective and growth-promoting effects of early and delayed nerve grafting following proximal seventh cervical spinal nerve (C7) axotomy were examined. The ventral branch of C7 spinal nerve was transected and axons projecting out of the proximal nerve stump were labelled with Fast Blue (FB). At the same time, the biceps brachii muscle was denervated by transecting the musculocutaneous nerve at its origin. Neuronal survival and muscle atrophy were then assessed at 1, 4, 8 and 16 weeks after permanent axotomy. In the experimental groups, a peripheral nerve graft was interposed between the transected C7 spinal nerve and the distal stump of the musculocutaneous nerve at 1 week [early nerve repair (ENR)] or 8 weeks [delayed nerve repair (DNR)] after axotomy. Sixteen weeks after nerve repair had been performed, a second tracer Fluoro-Ruby (FR) was applied distal to the graft to assess the efficacy of axonal regeneration. Counts of FB-labelled neurons revealed that axotomy did not induce any significant cell loss at 4 weeks, but 15% of motoneurons and 32% of sensory neurons died at 8 weeks after injury. At 16 weeks, the amount of cell loss in spinal cord and dorsal root ganglion (DRG) reached 29 and 50%, respectively. Both ENR and DNR prevented retrograde degeneration of spinal motoneurons and counteracted muscle atrophy, but failed to rescue sensory neurons. Due to substantial cell loss at 8 weeks, the number of FR-labelled neurons after DNR was significantly lower when compared to ENR. However, the proportion of regenerating neurons among surviving motoneurons and DRG neurons remained relatively constant indicating that neurons retained their regenerative capacity after prolonged axotomy. The results demonstrate that DNR could protect spinal motoneurons and reduce muscle atrophy, but had little effect on sensory DRG neurons. However, the efficacy of neuroprotection and axonal regeneration will be significantly affected by the amount of cell loss already presented at the time of nerve repair.

Animals↗

The localization and distribution of high affinity beta-nerve growth factor binding sites in the central nervous system of the adult rat. A light microscopic autoradiographic study using [125I]beta-nerve growth factor.

Although beta-nerve growth factor is primarily known for its trophic role in the peripheral nervous system, recent reports have also revealed an inductive effect of beta-nerve growth factor on the cholinergic metabolism of the forebrain. To learn more about the significance and location of beta-nerve growth factor action in the central nervous system, the distribution of [125I]beta-nerve growth factor binding sites was studied by using the method of in situ receptor autoradiography and compared with the distribution of acetylcholinesterase, a sensitive enzyme marker of cholinergic neurons. The autoradiographic studies demonstrated strong, specific and saturable [125I]beta-nerve growth factor binding to several neuronal groupings in the forebrain and brainstem. beta-Nerve growth factor binding sites and strong acetylcholinesterase reactivity were jointly distributed in the forebrain on the medial septal nucleus, the diagonal band of Broca, the magnocellular basal nucleus and in the striatum. In the brainstem, beta-nerve growth factor binding sites were located on a number of neuronal groups in the reticular formation, the dorsolateral lemniscus and the cochlear nuclei. In contrast to the forebrain, less correlation was found with the distribution of acetylcholinesterase; no beta-nerve growth factor receptor expression was recorded on the cholinergic motor nuclei of the brainstem, while specific [125I]beta-nerve growth factor labeling could be located on the non-cholinergic cochlear nuclei. The present autoradiographic studies reveal a variety of tentatively beta-nerve growth factor receptor-positive neurons in the central nervous system. While strong correlation between the cholinergic metabolism and the presence of specific beta-nerve growth factor binding is demonstrated in the forebrain, this observation could not be extended to the brainstem, indicating the chemical diversity of central beta-nerve growth factor receptor-positive neurons.

Acetylcholinesterase↗

Dorsal nerve root origins of the cutaneous nerves of the feline pelvic limb.

The dorsal root origins of cutaneous nerves supplying the feline pelvic limb were determined electrophysiologically in 11 cats. Cutaneous nerves were surgically exposed and the presence or absence of an evoked potential in response to stimulation of individual dorsal roots was noted. The dorsal cutaneous branches of L3-L5 and S3, and the lateral cutaneous branch of L3 each arose solely from their parent spinal nerves. The L7, S1, and S2 dorsal cutaneous branches had multiple dorsal root origins. The lateral cutaneous femoral nerve originated from L3-L6 dorsal roots in 4 patterns of origin, and the saphenous nerve originated from L4-L6 dorsal roots in 2 patterns of origin. The lateral and caudal cutaneous sural nerves originated from L6-S1 roots in 2 and 3 patterns, respectively. The lateral and medial plantar nerves arose from L6-S2 roots in 4 and 2 patterns, respectively. The superficial and deep peroneal nerves originated from L6-S1 roots in 2 and 3 patterns, respectively. The caudal cutaneous femoral nerve or its branches arose from L7-S3 in 8 origin patterns. The dorsal nerve of the penis and the superficial perineal nerve arose from L7-S3 and S1-S3 roots, respectively, each in 4 patterns. A subtle correlation between plexus type and dorsal root origins of the cutaneous nerves was noted.

Animals↗

Epidermal nerve fiber density and sural nerve morphometry in peripheral neuropathies.

OBJECTIVE: To study intraepidermal nerve fiber (IENF) density in distal leg skin biopsies, sural nerve morphometry, electrophysiology, and clinical features in patients with peripheral neuropathies. METHODS: We studied 26 patients with neuropathic complaints who had undergone clinical evaluation, nerve conduction studies, distal leg skin biopsy, and sural nerve biopsy. We quantified densities of IENF and of myelinated and unmyelinated fibers in the sural nerve. Associations among skin and sural nerve morphometric measures and sensory nerve action potential (SNAP) amplitudes were examined nonparametrically. Morphometric measures were examined with respect to diagnostic category of neuropathy. RESULTS: IENF density correlated with the densities of sural nerve total myelinated (r = 0.57, p = 0.0011), small myelinated (r = 0.53, p = 0.0029), and large myelinated fibers (r = 0.49, p = 0.0054). There was a trend toward an association between IENF and sural nerve unmyelinated fiber densities (r = 0.32, p = 0.054). Sural SNAP amplitude and large myelinated fiber densities were highly correlated (r = 0.87, p < 0.0001). IENF density and sural nerve small fiber measures were concordant in 73% of patients. Reduced IENF density was the only indicator of small fiber depletion in 23% of cases. It was usually normal in acquired demyelinating neuropathies and where clinical suspicion for neuropathy was low. CONCLUSIONS: Distal leg Intraepidermal nerve (IENF) density may be more sensitive than sural nerve biopsy in identifying small fiber sensory neuropathies. Assessments of IENF density and large fiber measures on biopsy and electrophysiology are both useful for characterizing sensory and sensorimotor neuropathies.

Action Potentials↗

[An experimental study on location and clinical application of recurrent laryngeal nerve in vagus nerve].

OBJECTIVE: To locate the recurrent laryngeal nerve fascicles in vagus and investigate the effect of latero-terminal neurorrhaphy to repair recurrent laryngeal nerve. METHOD: The method of dissection and acetylcholinesterase histochemical staining of neural fibers were used to locate the recurrent laryngeal nerve fascicles in vagus. Then 60 SD rats were divided into three groups. In experimental group right recurrent laryngeal nerve were incised and anastomosed to recurrent laryngeal nerve fascicles in vagus by means of latero-terminal neurorrhaphy. In control group right recurrent laryngeal were incised and sutured immediately by means of end-to-end nerve anastomosis. In normal group rats were not treated by any elements. One to three months later, 10 rats from each group were examined for vocal cord movement and nerve regeneration by using fibrolaryngscope and nerve electrormyography. RESULT: The recurrent laryngeal nerve fascicles is in the medial-front segment of the vagus and its diameter is about one-fourth as large as the vagus. One months after operation, This effect of latero-terminal neurorrhaphy had significant difference compared with the control group (P < 0.05). Three months after operation, This effect of latero-terminal neurorrhaphy had not significant difference compared with the control group (P > 0.05). CONCLUSION: The location of the recurrent laryngeal nerve fascicles in vagus provids important anatomical guideline for surgery. The latero-teminal neurorrhaphy has a similiar treatment effect compared with end-to-end nerve anastomosis. This microsurgical technique provides a new method for repairing recurrent laryngeal nerve.

Anastomosis, Surgical↗

Relationship between functional deficiencies and the contribution of myelin nerve fibers derived from L-4, L-5, and L-6 spinolumbar branches in adult rat sciatic nerve.

The distribution and relative intrafascicular contribution of myelin fibers derived from spinal segments L-4 to L-6 were analyzed in adult rat sciatic nerve and its main branches, using 200-kDa neurofilament subunit immunodetection in previously injured nerve sections in the L-4 or L-5 spinal branch or both. These branches' functional contribution was evaluated 16 days after the injury, using the method of J. Bain, S. Mackinnon, and D. Hunter (1988, Plast. Reconstr. Surg. 83: 129-136). A common topographic intrafascicular distribution was found in 69% of cases, with notable segregation of L-4 and L-5 fibers and a random distribution for L-6 fibers. At sciatic nerve main branch level, L-4 contributes almost entirely to the peroneal nerve, L-5 to the tibial nerve, and L-6 and other branches to the sural nerve. After injury to L-4, a significant reduction in peroneal nerve functional index (PFI) was observed, as was a reduction in print length (PL). Injury to L-5 caused a significant reduction in the sciatic (SFI) and tibial (TFI) functional nerve indices, an increase in PL, and a reduction in the spread between opposite toes (TS). Finally, transection of both L-4 and L-5 was followed by a significant reduction in all functional indices measured, an increase in PL, and a reduction in intermediate toe (ITS) and opposite toe spread (TS). The results indicate a direct relationship between the distribution and contribution of the spinal nerve fibers forming the sciatic nerve and the alteration in functional indices for sciatic, tibial, and peroneal nerves.

Animals↗

Facial nerve preservation during surgery for removal of acoustic nerve tumors.

A series of 33 patients with 35 acoustic nerve tumors is reviewed. Tumor size was estimated from computerized tomography (CT) scans, and its influence on anatomical and functional preservation of the facial nerve was assessed. Six tumors (one invading the petrous bone, three medium and two large tumors) were not detected on CT scans. The translabyrinthine approach was used in seven instances (one small and six medium tumors) and the suboccipital transmeatal approach for 28 tumors (seven medium and 21 large tumors). Anatomical preservation of the facial nerve was achieved in 83% of operations for tumor removal, two of which were subtotal. A further two patients underwent subtotal removal, but the facial nerve was destroyed. Large tumors carried an increased risk of damage to the facial nerve, but even in this group the nerve was preserved anatomically intact in 70% of cases. Damage to the facial nerve occurred more frequently in patients with preoperative evidence of facial weakness; however, this factor did not appear to influence functional recovery of the facial nerve, provided that the nerve was intact at the end of the operation. A simple grading system for facial nerve function is described. Ony 76% of anatomically intact facial nerves showed any evidence of function 1 month after surgery. Postoperatively, facial function improved with time. At the latest review, 45% of these patients had normal facial function or mild facial weakness (Grades I and II).

Adolescent↗

Pelvic nerve plexus trauma at radical hysterectomy and simple hysterectomy: the nerve content of the uterine supporting ligaments.

BACKGROUND: A major cause of the pelvic morbidity after a radical hysterectomy (RH) is thought to be damage to the pelvic nerve plexus, but direct evidence is lacking. We set out to determine the nerve content of the uterosacral ligaments (USLs) and cardinal ligaments (CLs) at the level at which they are divided during a radical hysterectomy and a simple hysterectomy. METHODS: Intraoperative cross-sectional biopsies were collected from the lateral third of the uterosacral ligaments (USLs) and cardinal ligaments (CLs) in 20 women undergoing radical hysterectomy (RH) and from the uterine insertion of these ligaments in 11 women undergoing a simple hysterectomy. Quantitative immunocytochemistry was utilized to demonstrate and quantify the nerve content of the uterine supporting ligaments at the level at which they are divided in a RH and in a simple hysterectomy. Indirect immunofluorescence staining of frozen cryostat sections was performed using primary antibodies to PGP 9.5 (a pan-neuronal marker). A computer-assisted image analyzer measured the percentage area of immunoreactivity (PAI) that was used to quantify the nerve density. Confocal microscopy was used to determine the composition and spatial arrangement of nerve fibers in the ligaments. RESULTS: The PAI was significantly greater in the RH biopsies than in the simple hysterectomy biopsies, for both the CLs (P < 0.001) and the USLs (P < 0.001). In the RH biopsies, more nerve tissue was present in the USL than CL (P = 0.01), and compared with the CL more of the nerve fibers in the USL were concentrated in large trunks. Excluding these trunks and autonomic ganglia, the free nerve content of the USL was lower than that of the CL (P < 0.001). The presence of nerve trunks, autonomic ganglia, and free nerve fibers within the lateral third of the USL and CL is consistent with extension of the inferior hypogastric plexus along these ligaments to the pelvic organs. CONCLUSIONS: The uterine supporting ligaments contain autonomic nerves and ganglia, as extensions of the inferior hypogastric plexus. The USLs have a greater nerve density than the CLs. Because RH disrupts more nerve tissue than a simple hysterectomy, these data provide further evidence for the neurogenic etiology of pelvic morbidity after RH.

Cross-Sectional Studies↗

A sympathetic projection from sacral paravertebral ganglia to the pelvic nerve and to postganglionic nerves on the surface of the urinary bladder and large intestine of the cat.

Anatomical and electrophysiological experiments have demonstrated a prominent projection from the sacral sympathetic chain via the pelvic nerve to postganglionic nerves on the surface of the urinary bladder and the large intestine of the cat. Retrograde labeling studies revealed that the pelvic nerve, which is generally believed to carry primarily parasympathetic axons, has a considerable population of sympathetic fibers originating mainly from the S1-S3 paravertebral ganglia. The number of sympathetic neurons projecting to the pelvic nerve (2,100) was about 75% of that projecting to the pudendal nerve (2,900), a somatic nerve which would be expected to carry a large sympathetic fiber constituent. Sympathetic neurons projecting to the pudendal nerve were located primarily in the L6-S2 ganglia. Electrophysiological studies confirmed the presence of a sympathetic pathway from the paravertebral ganglia to the pelvic viscera. Electrical stimulation (thresholds 1.5-3 V) of the lumbar sympathetic chain evoked firing in the pelvic nerve and in postganglionic nerves on the surface of the colon and bladder at latencies of 60-150 msec. The responses were unaffected by cutting the chain one segment rostral to the site of stimulation, but were abolished by the administration of a ganglionic-blocking agent (tetraethylammonium). The responses on the colon and bladder postganglionic nerves were also abolished by transection of the pelvic nerve. The conduction velocity in the sympathetic postganglionic axons was approximately 1 m/second. In summary, these studies indicate that the pelvic nerve, like somatic nerves, receives a prominent projection from the sympathetic chain ganglia. The function of this sympathetic paravertebral pathway and its relationship with prevertebral innervation of the pelvic organs remains to be established.

Adrenergic Fibers↗

Early experience with intraoperative cavernous nerve stimulation with penile tumescence monitoring to improve nerve sparing during radical prostatectomy.

OBJECTIVES: To determine if intraoperative stimulation of the cavernous nerves while monitoring changes in penile tumescence to map the course of these nerves would result in an improvement in nerve sparing and erectile function after radical prostatectomy. METHODS: Patients were eligible for this pilot study if they were undergoing a radical prostatectomy and were candidates for a nerve-sparing approach. Erectile function was assessed by patient self-reporting and questionnaire before surgery and by patient self-reporting periodically 12 months after surgery. A cavernous nerve stimulator and tumescence-monitoring device was used during radical prostatectomy to identify the course of the cavernous nerves and guide the surgeon in avoiding nerve damage. Patients were monitored for any evidence of complications and/or adverse events for 1 year from time of surgery. RESULTS: Twenty-six patients were recruited to the trial. Nerve stimulation and tumescence monitoring was performed in 23 patients. Twenty-one of 23 patients demonstrated a tumescence response to intraoperative nerve stimulation. Nineteen of 21 patients reported erectile function preoperatively. Seventeen (89%) of 19 patients demonstrated a tumescence response during surgery. Sixteen (94%) of the 17 patients who demonstrated a response to nerve stimulation and for whom the surgery was guided by the tumescence response reported the ability to have erections after surgery. No side effects due to the use of the device were reported. Only 3 (12%) of 25 patients had positive margins confined to the lateral margin and/or apex whose modifications associated with nerve sparing could conceivably have altered margin status. CONCLUSIONS: These clinical data suggest that an intraoperative tumescence response to cavernous nerve stimulation may guide the surgeon in preserving cavernous nerves and improving erectile function after radical prostatectomy.

Aged↗

Prediction of facial nerve function after surgery for cerebellopontine angle tumors: use of a facial nerve stimulator and monitor.

A series of 18 patients undergoing surgery for cerebellopontine angle tumors is reported. Patients were grouped according to size of tumor (0 to 2.5 cm, 11 cases; more than 2.5 cm, 7 cases). In all, the facial nerve was identified and conductance assessed by monitoring the facial electromyographic response to facial nerve stimulation. Postoperative facial nerve function was graded clinically after 3 months according to the House scale. Tumor removal was complete in all cases. In patients with tumors up to 2.5 cm the facial nerve was intact to visual inspection at the end of the procedure in all but one, where partial division was evident. In this group intraoperative facial nerve stimulation indicated electrical integrity in 8 of the 11 cases, all of which regained good facial nerve function postoperatively (House grades I and II). Nerve conduction was lost during the operation in the remaining three patients with small tumors; two subsequently developed a moderately severe (grade IV) dysfunction and the third, a total paralysis (grade VI). In the large (more than 2.5 cm) tumor group the facial nerve was anatomically intact in five of the seven cases, partially divided in one, and completely sectioned in the remaining case. Facial nerve stimulation indicated functional integrity in three patients, two of whom developed moderate (grade III) and the third a severe (grade V) dysfunction. In the other four cases nerve function could not be detected at operation; three of these developed a moderate facial nerve dysfunction (grade III/IV) and the final case a complete paralysis (grade VI). Intraoperative facial nerve monitoring appeared to predict eventual facial function accurately in the small tumor group, but did not predict facial nerve recovery reliably following surgery for larger tumors.

Journal Article↗

Regulation of interstitial cell differentiation in Hydra attenuata. VI. Positional pattern of nerve cell commitment is independent of local nerve cell density.

The interstitial cell of hydra is a multipotent stem cell, which produces nerve cells as one of its differentiated cell types. The amount of interstitial cell commitment to nerve differentiation varies in an axially dependent pattern along the body column. The distribution of nerve cell density has the same equivalent axial pattern. These facts have led to speculation that the regulation of nerve cell commitment is dictated by the nerve cell density. We examined this question by assaying interstitial cell commitment behaviour in 2 cases where the normal nerve cell density of the tissue had been perturbed: (1) in epithelial hydra in which no nerve cells were present; and (2) in hydra derived from regenerating-tip isolates in which the nerve density was increased nearly 4-fold. We found no evidence of regulation of nerve cell commitment in response to the abnormal nerve cell densities. However, the typical axial pattern of nerve commitment was still obtained in both sets of experiments, which suggests that interstitial cell commitment to nerve differentiation is dependent on some parameter of axial location that is not associated directly with the local nerve cell density.

Animals↗

[Morphological characteristics of the posterior brachial cutaneous nerve--a consideration of the development of cutaneous nerves in man].

The posterior brachial cutaneous nerve (Cbp) has certain characteristic features, being different from adjacent cutaneous nerves such as the medial brachial cutaneous nerve (Cbm) and the intercostobrachial nerve (Icb). These features are summarized as follows. 1) At the dorsal surface of the arm, the Cbp passes deeply beneath the fascia of the arm covering the dorsal surface of the long head of the triceps brachii, whereas the Cbm and the Icb pass superficial to it. In this area, the Cbp is accompanied in its course by a small artery. 2) The Cbp has no communication with the Cbm and the Icb on its way to the arm. 3) A precise and more detailed examination using a stereoscopic microscope reveals that the Cbp supplies the branches to the fascia of the dorsal surface of the arm, before passing through it. 4) The Cbp arises from the stem of the radial nerve forming a common trunk with the muscular branch to the long head of the triceps brachii. 5) In the brachial plexus, the Cbp is derived from segments C7 and C8, mainly the latter, and is composed of the most caudal elements of the radial nerve. According to the dermatome map, it would be unreasonable to consider that the Cbp (C8) is distributed in the skin, being intercalated between the Cbm (T1) and the Icb (T2). 6) Comparative anatomically, the Cbp cannot be observed in the monkey, dog, cat, rabbit or rat. Instead, in these animals, the muscular branch to the dorsoepitrochlearis arises from the radial nerve and takes the same course as that of the Cbp in man. According to Eisler (1901, 1912), when a muscle degenerates during the process of phylogeny or ontogeny, the supplying nerve sometimes remains in loco, as if representing the site where the muscle previously existed. As examples of these cases, Eisler described the following findings. 1) A fine branch arises from the loop of the cervical nerve and supplies the fascia, which extends between the clavicle and the omohyoid muscle. Eisler considered the fascia to be a remnant of the cleidohyoid muscle, which normally exists in lower mammals. 2) A branch sometimes arises from the lateral cutaneous branch of the upper intercostal nerve and passes along the ventral thoracic wall. Eisler considered this branch to be derived from the nerve supplying the external oblique abdominal muscle. 3) The interosseous nerve of the legs shows a remnant of the nerve supplying the pre-existing posterior interosseous muscle.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Unilateral hypoglossal nerve atrophy as a late complication of radiation therapy ofhead and neck carcinoma: a report of four cases and a review of the literature on peripheral and cranial nerve damages after radiation therapy.

The case histories of four patients who developed hemiatrophy of the tongue from 3 to9 years after a course of curative radiation therapy for carcinomas of the head and neck are presented. These patients subsequently followed for from 1 1/2 to 6 years withoutlocal recurrence of the tumor, distant metastasis, or involvement of other cranial nerves, indicative of only a unilateral hypoglossal nerve atrophy. A review of the literatureshowed that peripheral and cranial nerve damages after radiation therapy have been reported for the optic nerve, hypoglossal nerve, oculomotor nerve, abducens nerve, recurrent laryngeal nerve, brachial plexus nerves and peripheral nerves of the extremeties. Reviewof clinical and experimental data indicated that in most cases, the damages were probably caused by extensive connective tissue fibrosis around and infiltrating the nerve trunks. Three possible types of peripheral and cranial nerve damages after radiation therapy are identified.

Cranial Nerves↗

Stimulation of neurite outgrowth in a human nerve scaffold designed for peripheral nerve reconstruction.

The clinical outcome of microsurgical reconstruction of large peripheral nerve lesions depends on the availability of suitable graft material. Allogenic nerve grafts are rejected by the immune system. Extracellular-matrix proteins, in contrast to the resident cells, are of low immunogenicity in allografts. Here, human tibial nerve segments were extracted with lysophosphatidyl choline. The obtained cell-free and myelin-free scaffold consisted of empty endoneural tubes with maintained extracellular matrix architecture. The nerve scaffold had mechanical properties comparable to intact nerve, making it suitable for microsurgical reconstruction. Sections of the nerve scaffold were tested as a substrate for the adhesion and neuronal differentiation of human neuroblastoma-derived LAN-5 cells. Nerve extraction removed laminin-2, an isoform of laminin important for peripheral nerve regeneration. Laminin-2 reloading of the nerve scaffold did not improve cell adhesion and axon growth. Chemical crosslinking of heparan sulfate, on the other hand, increased the percentage of adherent cells with outgrowing neurites from 48 to 85%. Combined laminin-2 reloading and heparan sulfate crosslinking reduced the percentage of neurite-forming cells to 22% of the number of adherent cells. Implantation of the nerve scaffold into the peritoneal cavity of mice was not cytotoxic, and neovascularization of the graft material was observed within weeks. In conclusion, extraction of human nerve with detergents revealed a biocompatible nerve scaffold supporting neuronal cell adhesion. Heparan sulfate crosslinking to the scaffold surface improved neurite outgrowth, presumably mediated by midkine, a member of the neurokine family of growth factors, which is secreted by neuroblastoma-derived cells and binds to heparan sulfate.

Animals↗