Peripheral hypomyelinization in two golden retriever littermates

Peripheral hypomyelinization was found in 2 Golden Retriever littermates that had pelvic limb ataxia, depressed postural reactions, and depressed segmental reflexes. Diagnostic findings included infrequent denervation potentials, reduced or absent evoked potentials, and markedly diminished motor nerve conduction velocities. Light and electron microscopy of peripheral nerves revealed fewer than normal myelinated axons, myelinated sheaths inappropriately thin for the caliber of the fiber, poor myelin compaction, greater than normal numbers of Schwann cell nuclei, many Schwann cells with voluminous cytoplasm, and greater than normal amount of perineural collagen. Findings were compatible with a peripheral hypomyelinization process; a defect in Schwann cell function was suspected.     

A canine peripheral nerve sheath tumor including peripheral nerve fibers

Peripheral nerve sheath tumor was found in a 7-year-old male mongrel dog. The tumors were located in the right cheek subcutis and oral submucosa. Histologically, neoplastic cells were arranged in streaming bundles, occasionally interlacing bundles or whorls of elongated and spindle cells. Cellular atypia was poor and mitotic figures were rarely observed. Ultrastructurally, neoplastic cells had basement membrane, typical of Schwann cells. One bundle of normal peripheral nerve fibers and some myelinated axons were seen within the tumor tissues. Immunohistochemically, neoplastic cells reacted to vimentin, glial fibrillary acidic protein, S-100 protein and neuron specific enolase. In addition to the above immunoreactions, the included nerve fibers were positive for myelin basic protein and neurofilament protein. This paper also discusses immunohistochemical findings on differential diagnosis in comparison with those of canine hemangiopericytomas reported hitherto.     

An ultrastructural study of spinal nerve roots and dorsal root ganglia in aging rats with spontaneous radiculoneuropathy

The spinal nerve roots and dorsal ganglia of 104- to 135-week-old rats with spontaneous radiculoneuropathy were examined by light and electron microscopy. Demyelination was common in myelinated fibers of various diameters of both ventral and dorsal roots. The most striking alteration was wide distention of myelin sheaths, which extended throughout the entire internode. The spaces formed between separated lamellae frequently were invaded by macrophages. Subsequent vesicular degeneration of myelin seemed to be mediated by invading macrophages. These processes caused complete myelin destruction, but most axons showed no degenerative changes except for obvious reduction in diameter. Occasionally, there were clumping and partial degradation of neurofilaments and ruptured axolemma in the severely demyelinated axons. A few fibers also were undergoing wallerian-type degeneration, perhaps secondary to the severe demyelinative changes. Remyelinating fibers in various phases of repair were coexistent with markedly demyelinated ones. Demyelinative changes described above also developed within some of these remyelinated internodes. There were no remarkable changes in neurons of the dorsal root ganglia, though accumulation of lipofuscin was common. Our findings suggest that the changes in the nerve roots are essentially a primary segmental demyelination in aging rats with radiculoneuropathy.     

Equine laryngeal hemiplegia. Part II. An electron microscopic study of peripheral nerves

The recurrent laryngeal nerves were examined by electron microscopy in five control, four subclinical and four clinical laryngeal hemiplegic horses. In addition, the peroneal nerve was examined in two horses in the latter group. The distally distributed loss of large myelinated fibres in the left recurrent laryngeal nerve seen by light microscopy was confirmed. In addition, active axonal pathology was found to be more evident than indicated by light microscopic investigations. The onion bulb formations observed indicated the repetitive nature of the damaging influence to nerve fibres. Although the pathological changes were most obvious in the distal left recurrent laryngeal nerve, alterations similar in type and distribution were present in other areas of the left and right nerves, and in the distal hindlimb nerves. The observation of fibres with inappropriately thick myelin sheaths relative to their axonal calibre, was confirmed statistically by determining the regressions of axis cylinder perimeter against the number of myelin lamellae. In conclusion, the peripheral nerve pathology of equine laryngeal hemiplegia was demonstrated to be a distally distributed loss of myelinated fibres, with considerable active axonal damage, in conjunction with axonal atrophy. These features suggest that this disease may be classified as a distal axonopathy.     

Pathological aspects of Australian Stringhalt.

Nine horses with clinical signs of Australian Stringhalt were killed and tissues collected for a detailed pathological study. Lesions were limited to peripheral nerves and muscles. The most severely affected nerves were the superficial and deep peroneal, distal tibial, plantar digital, volar and recurrent laryngeal nerve with changes characterised by a selective loss of large diameter myelinated fibres with various degrees of demyelination, fibrosis, Schwann cell proliferation and onion-bulb formation. A routine evaluation of the brain and spinal cord by light microscopy failed to reveal any consistent abnormalities. Morphometric analysis of deep peroneal and recurrent laryngeal nerves confirmed the reduced number of large diameter myelinated axons. Teased fibre preparations of these nerves did not show any abnormalities in internodal distance. The most severe muscle lesions were in the long and lateral digital extensors, cranial tibial, dorsal cricoarytenoid, gracilis and lateral deep digital flexor with extensive atrophy of fibres and diffuse fibrosis. Histochemical evaluation of the long digital extensor from 3 affected horses showed an abnormally wide distribution in fibre size and a reduction in type II fibres compared with controls. These lesions are consistent with a distal axonopathy leading to neurogenic muscle atrophy. The distribution of neuromuscular lesions in Australian Stringhalt may be explained by the susceptibility of longer, larger myelinated nerve fibres to injury, but the cause for this distal axonopathy remains unknown.     

Morphometric Comparison between Controlateral Sciatic Nerves in the Male and Female Rabbit

Some morphometrical parameters of the axons making up the controlateral sciatic nerves, both in the male and female rabbits were calculated and compared by means of a Zeiss Vidas image analyser (Ober Kochen, Germany). The results show that the fibres constituting the left nerve have a greater mean diameter but a lower mean density than those constituting the right nerve. This suggests that the diameter of the myelinated fibres and the density of both the myelinated and unmyelinated fibres do not vary from male to female. On the other hand, the G ratio and the diameter of the unmyelinated axons do, since the nerves on the right side (in both sexes) have higher morphometric values, on average, than the controlateral ones.     

Structural and ultrastructural study of the intracranial portion of the oculomotor, trochlear and abducent nerves in dog

The right intracranial portion of the oculomotor, trochlear and abducent nerves were removed from six adult German shepherd dogs and analysed by light and electron microscopy. In all cases the nerve sectional area was calculated. Unmyelinated and myelinated fibres were analysed and number, diameter and cross-sectional area were calculated. In myelinated fibres, also calculated were the corresponding axon area and diameter, and myelin sheath thickness. The mean number of myelinated fibres was 8543.50 +/- 1231.85 being the unmyelinated 1402 +/- 241.58 in the oculomotor nerve; 1509 +/- 223.17 and 287.67 +/- 72.28 in the trochlear nerve and 2473.00 +/- 211.41 and 231.25 +/- 92.67 respectively in the abducent. The mean diameter was 10.23 +/- 0.68 microm in myelinated and 0.43 +/- 0.21 for unmyelinated in oculomotor nerve, 10.53 +/- 0.55 microm and 0.33 +/- 0.04 for the trochlear, and 10.45 +/- 1.27 microm and 0.47 +/- 0.09 in the abducent nerve respectively. This study reveals that oculomotor, trochlear and abducent nerves of the dog show structural and ultra-structural features similar to the same nerves in other species.     

Spongy degeneration of white matter in the central nervous system of silver foxes (Vulpes vulpes)

A disorder of central nervous white matter in Norwegian-bred silver foxes is described from the case histories of 21 clinically affected foxes. The main presenting sign of this disorder was caudal limb ataxia, which appeared between 2 1/2 and 4 months of age and progressed over the next 4-8 weeks. Only four affected foxes were allowed to live beyond this period, but they showed moderate to marked improvement. Light microscopic examination of specimens from 16 affected foxes necropsied between 3 1/2 and 6 1/2 months of age revealed lesions that were restricted to the white matter of brain and spinal cord. The lesions were characterized by a symmetrical spongy change with vacuoles of varying sizes and included significant myelin deficiency. There was a relative preservation of axons and nerve cells and no significant inflammation or vascular reaction. An astrocytic hypertrophy was usually associated with the spongy change. Ultrastructural examination of central nervous tissue from two, perfusion-fixed, 6-month-old foxes showed intramyelin vacuoles resulting from splitting of the myelin lamellae at the intraperiod line and was interpreted as indicating myelin edema. Expanded extracellular spaces and watery astrocytic processes also contributed to the vacuolar appearance. Astrocytic processes in affected areas were hypertrophic and contained abundant filaments. Although the 16 silver foxes had severe clinical signs, their lesions had features in common with the juvenile form of Canavan's disease in children and a spongy degeneration reported in Labrador Retrievers; however, the clinical course in the foxes was not uniformly progressive.     

Morphologic and immunohistochemical features of two spontaneous peripheral nerve tumors in Wistar rats

Morphologic features and S-100 protein immunoreactivity of a benign and malignant peripheral nerve sheath tumor were studied in two Wistar rats. Neoplasms that developed in untreated control rats from tumor bioassays were S-100 protein positive and had similar histopathologic features. Each peripheral nerve sheath tumor was encapsulated and composed of spindle cells arranged around small thin-walled blood vessels. Palisaded tumor cells were in the benign peripheral nerve sheath tumor while cells of the malignant peripheral nerve sheath tumor had cellular atypia and moderate numbers of mitoses. Ultrastructural examination of the malignant peripheral nerve sheath tumor revealed cells with external lamina and interdigitation of cytoplasmic processes. Intracytoplasmic concentric lamellae were seen; they were regularly spaced with a periodicity of about 15 nm. Such structures, indistinguishable from myelin sheaths, have not been commonly associated with peripheral nerve sheath tumors in man. Electron microscopy and immunohistochemistry were useful in the diagnosis of these tumors as Schwannomas and in differentiation from other spindle cell tumors.     

神经生长因子及其受体TrKA在山羊脊髓发育中的表达特点

运用免疫组织化学超敏 SP法对山羊胎儿脊髓发育中神经生长因子 (nerve growth factor,NGF)及其高亲和力受体 Tr KA的表达及其功能进行了系统的研究和探讨。结果显示 ,山羊胎儿脊髓灰质中存在 NGF及其受体 Tr KA,于 6周龄胚就可检测到 ,随胚龄增加 ,其表达范围及免疫反应着色程度逐渐增强。 NGF主要分布于腹角和背角的神经细胞 ,反应产物主要定位于胞质和突起 ;Tr KA的分布主要以腹角及胶状质为主 ,反应产物主要定位于胞核 ,后期胞质及突起也可见到阳性反应。在山羊胎儿脊髓白质中也可观察到 NGF及 Tr KA免疫阳性反应 ,其发育后期更为显著 ,阳性反应主要分布于神经胶质细胞核、神经纤维的轴索及雪旺氏细胞。结果提示 ,NGF不仅对交感和感觉神经元的发育起作用 ,而且还与腹角运动神经元的发育有关     

Tumor-specific diagnostic marker for transmissible facial tumors of Tasmanian devils: immunohistochemistry studies

Devil facial tumor disease (DFTD) is a transmissible neoplasm that is threatening the survival of the Tasmanian devil. Genetic analyses have indicated that the disease is a peripheral nerve sheath neoplasm of Schwann cell origin. DFTD cells express genes characteristic of myelinating Schwann cells, and periaxin, a Schwann cell protein, has been proposed as a marker for the disease. Diagnosis of DFTD is currently based on histopathology, cytogenetics, and clinical appearance of the disease in affected animals. As devils are susceptible to a variety of neoplastic processes, a specific diagnostic test is required to differentiate DFTD from cancers of similar morphological appearance. This study presents a thorough examination of the expression of a set of Schwann cell and other neural crest markers in DFTD tumors and normal devil tissues. Samples from 20 primary DFTD tumors and 10 DFTD metastases were evaluated by immunohistochemistry for the expression of periaxin, S100 protein, peripheral myelin protein 22, nerve growth factor receptor, nestin, neuron specific enolase, chromogranin A, and myelin basic protein. Of these, periaxin was confirmed as the most sensitive and specific marker, labeling the majority of DFTD cells in 100% of primary DFTD tumors and DFTD metastases. In normal tissues, periaxin showed specificity for Schwann cells in peripheral nerve bundles. This marker was then evaluated in cultured devil Schwann cells, DFTD cell lines, and xenografted DFTD tumors. Periaxin expression was maintained in all these models, validating its utility as a diagnostic marker for the disease.     

雏鸡“卷趾”麻痹症坐骨神经病变观察

１７只１日龄肉用小公鸡,饲喂低水平核黄素日粮（１．６５ｍｇ／ｋｇ）,于２２－２３日龄间有２９．４％出现其型的“卷趾”麻痹症状。光镜观察,坐骨神经纤维雪旺氏细胞肿大、增生、酸性磷酶活性增强和髓鞘变性。严重病例的坐骨神经显著肿大,神经纤维分离,间质水肿和炎性细胞浸润。电镜观察,坐骨神经有髓神经纤维的髓鞘扭曲、分层、破碎、形成同心圆层状小体,神经轴膜与髓鞘分离形成间和神经轴索变形。雪旺氏细胞胞浆中见同心     

雏鸡核黄素缺乏症的外周神经酶细胞化学

为进一步探讨核黄素缺乏时外周神经变化的发生机理,对琥珀酸脱氢酶、酸性磷酸酶、腺苷三磷酸酶、碱性磷酸酶进行了酶细胞化学研究。结果表明,核黄素不足的鸡,雪旺氏细胞和轴突中琥珀酸脱氢酶活性下降,酸性磷酸酶活性明显升高,定位于雪旺氏细胞膜上的腺苷三磷酸酶和碱性磷酸酶活性均下降。通过对琥珀酸脱氢酶、腺苷三磷酸酶、碱性磷酸酶活性变化的动态观察,证明轻症鸡自愈的现象以及雪旺氏细胞中琥珀酸脱氢酶活性下降可能是形成脱髓鞘、外周神经水肿、导致雪旺氏细胞膜上的腺苷三磷酸酶和碱性磷酸酶活性下降的原因之一,而增生的雪旺氏细胞中琥珀酸脱氢酶活性增强则可能是修复损伤的一种代偿。腺苷三磷酸酶活性下降与神经水肿密切相关。     

雪旺氏细胞在外周神经损伤修复中的作用

实验结果表明，雪旺氏细胞在外周神经损伤修复中具有明显的吞噬变性髓鞘碎片的功能。表现在Ｍａｒｃｈｉ氏饿酸染色，大量的雪旺氏细胞浆内充满嗜饿酸颗粒，电镜下与之相应的是，发生变性的有髓神经纤维外的雪旺氏细胞内，含有大量的吞噬了髓鞘碎片的次级溶酶体，同时作为溶酶体标记酶的ＡＣＰ活性明显升高，吞噬消化功能加强。吞噬的目的可能在于清除变性髓鞘，促进髓鞘、轴突再生。     

Evaluation of Tissue Adhesive to Contain Axonal Regeneration in Horses

Bilateral palmar and plantar digital neurectomies were completed in 10 horses (a total of 80 neurectomies) using one of three methods: (1) simple transection (guillotine method); (2) epineural capping; (3) n-butyl cyanoacrylate injected into the epineural sheath to act as a nerve sealant. Horses were regularly evaluated clinically for tenderness in and around the surgical site, as well as skin sensation at the coronary band in the heel region, during the 12-week course of the study. None of the surgical sites exhibited any signs of drainage or infection. Horses were then euthanatized, the nerve stumps were dissected from surrounding tissues, and the length and width of the tissue mass that had formed on the end of the nerve was recorded. Longitudinal and transverse sections of the nerve endings were examined histologically for numbers of proliferating axon sprouts (neuroma formation); whether the axons had penetrated the epineurium; degree of Schwann cell proliferation; degree of chronic inflammation; extent of foreign body reaction; extent of retrograde degeneration of the nerve bundles; and amount of fibro vascular proliferation. The proportion of legs exhibiting tenderness or heel sensation did not differ significantly between the three different treatments at any of the six different times they were examined. There was no difference between the three treatments in the length or width of the fibrous tissue scar on the ends of the nerves or in the number of sprouting axons from the ends of the nerves. Of 80 nerves examined, only two nerves were not confined to the epineurium. Both these nerves had been treated by simple transection. Statistically there was more chronic inflammation and foreign body reaction in the acrylic treated nerves, but no difference in Schwann cell proliferation or retrograde degeneration between the three treatments. There was slightly less fibrovascular proliferation in the transected nerves than in those subjected to epineural capping or acrylic, but the difference was not statistically significant. The use of the tissue adhesive n-butyl cyanoacrylate to prevent the continuous growth of axons after digital neurectomy seems to offer little advantage over more traditional methods of neurectomy.     

Sensory and motor neuropathy in a Border Collie

A 5-month-old female Border Collie was evaluated because of progressive hind limb ataxia. The predominant clinical findings suggested a sensory neuropathy. Sensory nerve conduction velocity was absent in the tibial, common peroneal, and radial nerves and was decreased in the ulnar nerve; motor nerve conduction velocity was decreased in the tibial, common peroneal, and ulnar nerves. Histologic examination of nerve biopsy specimens revealed considerable nerve fiber depletion; some tissue sections had myelin ovoids, foamy macrophages, and axonal degeneration in remaining fibers. Marked depletion of most myelinated fibers within the peroneal nerve (a mixed sensory and motor nerve) supported the electrodiagnostic findings indicative of sensorimotor neuropathy. Progressive deterioration in motor function occurred over the following 19 months until the dog was euthanatized. A hereditary link was not established, but a littermate was similarly affected. The hereditary characteristic of this disease requires further investigation.     

Quantitative studies of the optic nerve fiber layer in the chicken retina.

The optic nerve fiber layer (NFL) of the chicken retina was studied quantitatively and morphologically at 17 positions along seven radially arranged bands from the dorsal tip of the pecten oculi using electron microscopy. The number of nerve fibers was counted in areas 6 microm in width x the full thickness of the NFL. Myelinated nerve fibers in the NFL were also identified immunohistochemically using anti-myelin basic protein serum. The dorsal area (dorsal, dorso-temporal and dorso-nasal bands) in the retina had thin NFL and contained the largest number of nerve fibers, which were mainly thin and unmyelinated. The ventral area (ventral and ventro-temporal bands) had a thick NFL and contained a relatively small number of nerve fibers, many of which were myelinated. The nasal band had the thickest NFL and contained as many nerve fibers as the dorsal area, with the temporal band showing a high ratio of myelinated fibers. The band had a thick NFL and contained many nerve fibers with a relatively low ratio of myelinated fibers. The relationship between the number and composition of nerve fibers in the NFL to the chicken visual characteristics was discussed. Although the myelin in the chicken retina was loose type, the myelin-forming cells were similar in appearance to dense oligodendrocytes. retina, morphometry, myelinated fiber, nerve fiber layer.     

Preferential denervation of the adductor muscles of the equine larynx. II: Nerve pathology

The terminal branches of the recurrent laryngeal nerve (RLN) of three normal ponies and six horses with sub-clinical laryngeal disease were examined qualitatively and quantitatively in an attempt to explain the preferential denervation of the laryngeal adductor muscles in the neuropathy of idiopathic laryngeal hemiplegia (ILH). The myelinated fibre spectra of all the motor nerve fibres in the left and right abductor and adductor branches of the RLN in three normal ponies were measured. The density of myelinated fibres was also calculated. There was no significant difference between the larger group of myelinated fibres in the adductor or abductor branches. In the six horses with laryngeal hemiparesis, however, there was a marked preferential loss of the medium/large size myelinated fibres in the left adductor branch, although nerve fibre densities were not significantly different. While no simple morphometrical feature was found to explain the selective muscle denervation, the greater loss of large diameter myelinated fibres in the adductor branches confirms the earlier observation of adductor muscle susceptibility in the neuropathy of ILH.     

Determination of functional and morphologic changes in palmar digital nerves after nonfocused extracorporeal shock wave treatment in horses

OBJECTIVE: To determine functional and morphologic changes in palmar digital nerves after nonfocused extracorporeal shock wave (ESW) treatment in horses. ANIMALS: 6 horses. PROCEDURES: The medial and lateral palmar digital nerves of the left forelimb were treated with nonfocused ESWs. The medial palmar digital nerve of the right forelimb served as a nontreated control nerve. At 3, 7, and 35 days after treatment, respectively, 2 horses each were anesthetized and nerves were surgically exposed. Sensory nerve conduction velocities (SNCVs) of treated and control nerves were recorded, after which palmar digital neurectomies were performed. Morphologic changes in nerves were assessed via transmission electron microscopy. RESULTS: Significantly lower SNCV in treated medial and lateral nerves, compared with control nerves, was found 3 and 7 days after treatment. A significantly lower SNCV was detected in treated medial but not lateral nerves 35 days after treatment. Transmission electron microscopy of treated nerves revealed disruption of the myelin sheath with no evidence of damage to Schwann cell bodies or axons, 3, 7, and 35 days after treatment. CONCLUSIONS AND CLINICAL RELEVANCE: Nonfocused ESW treatment of the metacarpophalangeal area resulted in lower SNCV in palmar digital nerves. This effect likely contributes to the post-treatment analgesia observed in horses and may result in altered peripheral pain perception. Horses with preexisting lesions may be at greater risk of sustaining catastrophic injuries when exercised after treatment.