Degeneration Of Myelinated Axons Research Articles

Prolonged Codeine Administration Causes Degeneration of Myelinated Axons and Motor Dysfunction in Wistar Rats.

Over-the-counter (OTC) anti-cough medications which contain codeine (an opioid) are extensively available in Nigeria, and hence prone to overuse or abuse. The study aimed to understand the effects of oral codeine administration on the integrity of neurons of the cerebral cortex and cerebellum and its behavioral implications in male Wistar rats. Thirty adult male Wistar rats of comparable weights were obtained and randomly allocated into 5 groups: A, B, C, D, and E (n = 6). Drugs used for the study were ArchilinTM with codeine and dihydrocodeine 30mg. Group A served as control and was administered 0.5mL/kg of normal saline. Groups B and C were treated with 1mg/kg and 2mg/kg of dihydrocodeine, respectively; Group D and E received 2mL/kg and 4mL/kg of ArchilinTM codeine syrup, respectively. The ArchilinTM codeine syrup and dihydrocodeine solutions were administered to the animals based on their body weight, orally and daily with the aid of oropharyngeal tubes for 21 days. The experimental animals were subjected to neurobehavioral studies using beam walk and open field. At the end of the treatment period, the animals were anesthetized with ketamine-hydrochloride intraperitoneally. The brains were quickly dissected out, rinsed with normal saline, and tissue processed for myelin studies. The beam walking and open field result revealed that prolonged codeine administration interfered with motor function in the experimental animals. Sections of the prefrontal cortex and cerebellum of rats given normal saline showed normal myelin sheaths, whereas animals in the treatment group showed degenerating myelin compared to the control. Prolonged consumption of prescription codeine causes degeneration of the myelin sheaths and this may affect the conduction of electrical impulses in myelinated axons thus resulting in motor function insufficiency.

Loss of Corticostriatal Mu-Opioid Receptors in α-Synuclein Transgenic Mouse Brains.

Ultrastructural, neurochemical, and molecular alterations within the striatum are associated with the onset and progression of Parkinson’s disease (PD). In PD, the dopamine-containing neurons in the substantia nigra pars compacta (SNc) degenerate and reduce dopamine-containing innervations to the striatum. The loss of striatal dopamine is associated with enhanced corticostriatal glutamatergic plasticity at the early stages of PD. However, with disease progression, the glutamatergic corticostriatal white matter tracts (WMTs) also degenerate. We analyzed the levels of Mu opioid receptors (MORs) in the corticostriatal WMTs, as a function of α-Synuclein (α-Syn) toxicity in transgenic mouse brains. Our data show an age-dependent loss of MOR expression levels in the striatum and specifically, within the caudal striatal WMTs in α-Syn tg mouse brains. The loss of MOR expression is associated with degeneration of the myelinated axons that are localized within the corticostriatal WMTs. In brains affected with late stages of PD, we detect evidence confirming the degeneration of myelinated axons within the corticostriatal WMTs. We conclude that loss of corticostriatal MOR expression is associated with degeneration of corticostriatal WMT in α-Syn tg mice, modeling PD.

Cerebrospinal fluid biomarkers of neurofibrillary tangles and synaptic dysfunction are associated with longitudinal decline in white matter connectivity: A multi-resolution graph analysis.

In addition to the development of beta amyloid plaques and neurofibrillary tangles, Alzheimer's disease (AD) involves the loss of connecting structures including degeneration of myelinated axons and synaptic connections. However, the extent to which white matter tracts change longitudinally, particularly in the asymptomatic, preclinical stage of AD, remains poorly characterized. In this study we used a novel graph wavelet algorithm to determine the extent to which microstructural brain changes evolve in concert with the development of AD neuropathology as observed using CSF biomarkers. A total of 118 participants with at least two diffusion tensor imaging (DTI) scans and one lumbar puncture for CSF were selected from two observational and longitudinally followed cohorts. CSF was assayed for pathology specific to AD (Aβ42 and phosphorylated-tau), neurodegeneration (total-tau), axonal degeneration (neurofilament light chain protein; NFL), and synaptic degeneration (neurogranin). Tractography was performed on DTI scans to obtain structural connectivity networks with 160 nodes where the nodes correspond to specific brain regions of interest (ROIs) and their connections were defined by DTI metrics (i.e., fractional anisotropy (FA) and mean diffusivity (MD)). For the analysis, we adopted a multi-resolution graph wavelet technique called Wavelet Connectivity Signature (WaCS) which derives higher order representations from DTI metrics at each brain connection. Our statistical analysis showed interactions between the CSF measures and the MRI time interval, such that elevated CSF biomarkers and longer time were associated with greater longitudinal changes in white matter microstructure (decreasing FA and increasing MD). Specifically, we detected a total of 17 fiber tracts whose WaCS representations showed an association between longitudinal decline in white matter microstructure and both CSF p-tau and neurogranin. While development of neurofibrillary tangles and synaptic degeneration are cortical phenomena, the results show that they are also associated with degeneration of underlying white matter tracts, a process which may eventually play a role in the development of cognitive decline and dementia.

Spinal cord degeneration in juvenile and adult swine

Spinal cord degeneration was identified in nine swine consisting of four fattening pigs (5 months old) and five adult sows (2 to 3 years old). These animals were raised on nine different farms and culled over a 1.5-year period on account of similar clinical signs encompassing ataxia and paresis progressing to paraplegia. Histopathologically, the spinal cord exhibited white matter degeneration with no predilection for specific tracts, which was more severe in five swine and less severe in the others. White matter lesions were characterized by Wallerian-type degeneration of myelinated axons, exhibiting axonal swelling/loss and myelin sheath dilation/disintegration associated with occasional macrophage reaction and little fibrous astrogliosis. Gray horn neurons were unremarkable. In the brain examined in three cases, similar but minimal degenerative lesions were observed in the marginal areas of the brainstem in one case. Significant lesions were absent in the hind limb nerves, including sciatic nerve, femoral nerve, and obturator nerve, in seven cases. The spinal lesions were regarded as being a variant of neurodegenerative disorder. The pathogenesis appeared to involve a primary impairment of myelinated axons in the spinal white matter (central axonopathy). The pattern and extent of this disease were considered different from those reported previously in swine with neurodegenerative or myelinopathic disorders of inherited, toxic, or nutritional origin. The etiology remains unknown, though a metabolic abnormality was suspected to be one of the likeliest possibilities.

Prevention of vincristine-induced peripheral neuropathy by genetic deletion of SARM1 in mice.

Peripheral polyneuropathy is a common and dose-limiting side effect of many important chemotherapeutic agents. Most such neuropathies are characterized by early axonal degeneration, yet therapies that inhibit this axonal destruction process do not currently exist. Recently, we and others discovered that genetic deletion of SARM1 (sterile alpha and TIR motif containing protein 1) dramatically protects axons from degeneration after axotomy in mice. This finding fuels hope that inhibition of SARM1 or its downstream components can be used therapeutically in patients threatened by axonal loss. However, axon loss in most neuropathies, including chemotherapy-induced peripheral neuropathy, is the result of subacute/chronic processes that may be regulated differently than the acute, one time insult of axotomy. Here we evaluate if genetic deletion of SARM1 decreases axonal degeneration in a mouse model of neuropathy induced by the chemotherapeutic agent vincristine. In wild-type mice, 4 weeks of twice-weekly intraperitoneal injections of 1.5 mg/kg vincristine cause pronounced mechanical and heat hyperalgesia, a significant decrease in tail compound nerve action potential amplitude, loss of intraepidermal nerve fibres and significant degeneration of myelinated axons in both the distal sural nerve and nerves of the toe. Neither the proximal sural nerve nor the motor tibial nerve exhibit axon loss. These findings are consistent with the development of a distal, sensory predominant axonal polyneuropathy that mimics vincristine-induced peripheral polyneuropathy in humans. Using the same regimen of vincristine treatment in SARM1 knockout mice, the development of mechanical and heat hyperalgesia is blocked and the loss in tail compound nerve action potential amplitude is prevented. Moreover, SARM1 knockout mice do not lose unmyelinated fibres in the skin or myelinated axons in the sural nerve and toe after vincristine. Hence, genetic deletion of SARM1 blocks the development of vincristine-induced peripheral polyneuropathy in mice. Our results reveal that subacute/chronic axon loss induced by vincristine occurs via a SARM1 mediated axonal destruction pathway, and that blocking this pathway prevents the development of vincristine-induced peripheral polyneuropathy. These findings, in conjunction with previous studies with axotomy and traumatic brain injury, establish SARM1 as the central determinant of a fundamental axonal degeneration pathway that is activated by diverse insults. We suggest that targeting SARM1 or its downstream effectors may be a viable therapeutic option to prevent vincristine-induced peripheral polyneuropathy and possibly other peripheral polyneuropathies.

Role of Pomegranate Juice and Atorvastatin in Ameliorating Spinal Neurotoxicity of Wistar Rats Maternally Fed on Hypercholesterolemic Diet

Background: The contribution of high dietary cholesterol to encephalomyelitis and retinal diseases give more attention to overcome its neurotoxicity. These led physician and scientists of using anti-lepidemic statin drugs, however their long-term treatment may develop complication. Today many views recommended supplements of natural products especially fruit to get demand of needed antioxidant to scavenge bad free radicals liberated from inflammation. Pomegranate juice supplementation is used in the present study in combination with atorvastatin drug hoping to give synergistic effects and improve neurotoxicity. Material and methods: Eighty pregnant Wistar albino rats weighing 180 g to 200 g body weight were used. They were arranged into eight groups (n=8) such as control, atorvastatin (1 mg/kg), pomegranate (0.5 ml 50%/ rat), atorvastatin and pomegranate, hyper ccholesterolemic group (3% cholesterol diet for 6 weeks before onset of gestation), hypercholesterolemia and atorvastatin and/or pomegranate. All treatments were maintained throughout gestation and lactation period till 2 and 3 week-old. Offspring were sacrificed by diethyl ether and their cervical spinal cord were dissected and separated. The spinal cord was subjected for histological and transmission electron microscopical investigations, biochemical assays of neurotransmitters (dopamine, serotonin and γ-Aminobutyric acid), vascular endothelial growth factors, 8-hydroxydeoxyguanosine, caspase 3 and caspase 7 as well as comet assay). Results: The present findings revealed massive cell death and necrosis within ependymal canal as well as pyknosis and edematous lesions of neuronal cells in offspring of hypercholesterolemic mothers. At ultrastructural level, there is a detected demyelination and vacuolar degeneration of myelinated axons. Many of sensory and motor neuronal cells exhibited compacted chromatin materials of their nuclei. These were associated with depletion of assayed neurotransmitters (DA and 5-HT), overexpression of vascular endothelial growth factors, caspases 3 and 7 and 8-hydroxydeoxyguanosine. Stretched DNA damage (comet assay) with obvious head and tail region was detected in neuronal cells of offspring of hypercholesterolemic mothers and decreased post-pomegranatesupplementation. Atorvastatin and pomegranate supplementation exhibited apparent improvement comparing with single atorvastatin or pomegranate manifesting highly synergistic effects. Conclusion: Feeding pregnant on hypercholesterolemic diet induced spinal cord injury of their offspring and these can be improved by pomegranate juice supplementation in combination with atorvastatin- treatment.

The effects of aminoguanidine, methylprednisolone, and melatonin on nerve recovery in peripheral facial nerve neurorrhaphy.

The medications may enhance the recovery after nerve paralysis. We aimed to evaluate the effects of aminoguanidine (AG), melatonin, and methylprednisolone on peripheral facial nerve neurorrhaphy. The buccal branch of the facial nerve was transected and autografted in 32 New Zealand rabbits. Subjects were divided into 4 groups equally (AG, melatonin, methylprednisolone, and control). After the medical treatment latency and amplitude were measured with nerve conduction study at 3, 6, and 10 weeks. Then, coapted segments of nerve were examined microscopically. The groups were compared with each other. The latent period was shortened, and the amplitudes were increased in the AG group; the latent period was shortened, and the amplitudes did not show significant change in the melatonin group with the time. There were no significant differences between the amplitudes at 3 to 6 and 3 to 10 weeks in the methylprednisolone group, and the latent period was shortened. There was no significant difference between the amplitude values at 3, 6, and 10 weeks in the control group. In the histological examination, AG had the best influence on preventing myelin degeneration and reducing the accumulation of myelin debris. Considering the increase in collagen fibers, the best results were achieved in the melatonin group. The degree of myelin-axonal degeneration was higher in the methylprednisolone group. The degree of collagen fiber increase, axonal degeneration, myelin degeneration, and the accumulation of myelin debris were detected quite high in the control group. Aminoguanidine and melatonin alone achieved an increase in regeneration after peripheral facial nerve neurorrhaphy, but methylprednisolone did not. The best healing was determined in the AG group.

Dorsal root compression produces myelinated axonal degeneration near the biomechanical thresholds for mechanical behavioral hypersensitivity

Increased sensitivity to mechanical stimuli produced by transient cervical nerve root compression is dependent on the severity of applied load. In addition, trauma in the nervous system induces local inflammation, Wallerian degeneration, and a host of other degenerative processes leading to axonal dysfunction. Here, axonal degeneration and inflammation were assessed following transient dorsal root compression to establish a relationship between conditions for dorsal root axonal changes and those previously established for the onset and maintenance of mechanical behavioral hypersensitivity (26.3 mN and 38.2 mN, respectively). Compression loads were applied over a range (0–110 mN) known to produce sustained behavioral hypersensitivity. CD68- and NF200-immunoreactivity, as well as axonal pathological changes, were assessed in the dorsal root to investigate the load thresholds requisite for inducing macrophage infiltration and axonal degeneration relative to those thresholds for producing the onset and persistence of behavioral hypersensitivity. Neurofilament accumulation and the depletion of NF200-immunoreactivity in the region of compressed tissue were produced for loads that produce mechanical behavioral hypersensitivity. A 50th-percentile load threshold was determined (31.6 mN) governing the onset of NF200 depletion. However, CD68-immunoreactivity was increased for nearly all loads, suggesting that macrophage recruitment may not be directly related to nerve root-mediated behavioral hypersensitivity. This study provides new evidence for threshold-mediated degenerative changes in the context of behavioral hypersensitivity following nerve root compression.

Evolution of a neuroprotective function of central nervous system myelin

The central nervous system (CNS) of terrestrial vertebrates underwent a prominent molecular change when a tetraspan membrane protein, myelin proteolipid protein (PLP), replaced the type I integral membrane protein, P0, as the major protein of myelin. To investigate possible reasons for this molecular switch, we genetically engineered mice to express P0 instead of PLP in CNS myelin. In the absence of PLP, the ancestral P0 provided a periodicity to mouse compact CNS myelin that was identical to mouse PNS myelin, where P0 is the major structural protein today. The PLP–P0 shift resulted in reduced myelin internode length, degeneration of myelinated axons, severe neurological disability, and a 50% reduction in lifespan. Mice with equal amounts of P0 and PLP in CNS myelin had a normal lifespan and no axonal degeneration. These data support the hypothesis that the P0–PLP shift during vertebrate evolution provided a vital neuroprotective function to myelin-forming CNS glia.

Metastasis-associated Mts1 (S100A4) protein is selectively expressed in white matter astrocytes and is up-regulated after peripheral nerve or dorsal root injury

The S100 family of calcium binding proteins has been shown to be involved in a variety of physiological functions, such as regulation of enzyme function, cell motility, modification of extracellular matrix, and cell proliferation. Several members of the S100 family are expressed in the nervous system, but their functional roles are still largely obscure. The Mts1 gene codes for the S100A4 protein, which has been implicated in the control of cell proliferation and metastasis activity of tumor cells. We have used immunohistochemistry to examine the expression pattern of the Mts1 protein in the adult rat spinal cord and how this expression is influenced by peripheral nerve or dorsal root injury. Mts1 immunoreactivity (IR) was present only in white matter astrocytes in the intact spinal cord. Sciatic nerve as well as dorsal root injury induced a marked and prolonged up-regulation of Mts1-IR in astrocytes in the region of the dorsal funiculus containing the central processes of the injured primary sensory neurons. These findings suggest that Mts1 plays a unique physiological role in white matter astrocytes as well as in the response of astrocytes to degeneration of myelinated axons.

Selective degeneration of dorsal root ganglia and dorsal nerve roots in methyl mercury-intoxicated rats: a stereological study.

The components of the nervous system of rats that are most critically affected by methyl mercury are still a matter of debate. A recent stereological study of rats with typical symptoms resulting from methyl mercury intoxication demonstrated that the morphology of cerebellar granule cells and Purkinje cells were unchanged at the light microscopic level, even though there was pronounced degeneration of myelinated axons in dorsal nerve root nerves. In the present study, unbiased stereological methods were used to quantify morphological changes in the dorsal root ganglion, and dorsal and ventral nerve roots of the rats used in the previous study. The rats were treated with methyl mercury (2 mg daily/kg, per os) for a 19-day period that was followed by a 32-day period without treatment. The means of the total numbers of A-cell and B-cell perikarya in the dorsal root ganglion of the intoxicated rats were reduced by 60% and 24%, respectively. The mean volume of A-cell perikarya in rats of the experimental group was reduced by 22%, whereas the mean volume of B-cell perikarya was the same in the two groups. In the experimental group, the total number of myelinated axons in the dorsal nerve roots was reduced by 60%, whereas no difference was found in the ventral nerve roots. The areas of axon and myelin sheath, dorsal and ventral nerve roots were not affected. This study demonstrates that extensive loss of dorsal root ganglion cells and myelinated axons in dorsal nerve roots precedes light microscopical changes in the ventral nerve roots and the cerebellum of rats intoxicated with methyl mercury.

Spinal accessory nerve biopsy as an ante mortem diagnostic test for equine motor neuron disease.

The effectiveness of spinal accessory nerve branch biopsy evaluation as a means to confirm the diagnosis of equine motor neuron disease (EMND) was investigated. Sixteen horses with histories and clinical signs suggestive of EMND and 16 control horses with neither histories nor clinical signs of any neurological disorder, were subjects of the study. Biopsy samples of the ventral branch of the spinal accessory nerve were obtained either surgically, under general anaesthesia or post mortem immediately after euthanasia. Evaluation was done on the spinal cord of all horses to serve as the definitive diagnostic indicator of EMND. Results indicate that biopsy of the ventral branch of the spinal accessory nerve is a reliable ante mortem diagnostic test for EMND. Histological evidence of the degeneration of myelinated axons is present in both acute and arrested cases. The ventral branch of the spinal accessory nerve is easy to approach surgically and biopsy of the nerve causes no disfigurement of the sternocephalicus muscle. The use of semi-thin Epon sections is an excellent method of sample preparation. Formalin fixation and routine paraffin embedment may prove more accessible and provide good quality preparations for reliable interpretation. In the hands of an experienced pathologist, the sensitivity and specificity reliability coefficients for spinal accessory nerve branch biopsy are 94%, making this technique an extremely valuable diagnostic tool for the ante mortem diagnosis of EMND.

Bcl-2 overexpression prevents motoneuron cell body loss but not axonal degeneration in a mouse model of a neurodegenerative disease

Bcl-2 and its analogs protect different classes of neurons from apoptosis in several experimental situations. These proteins may therefore provide a means for treatment of neurodegenerative diseases. We examined the effects of Bcl-2 overexpression in a genetic mouse model with motor neuron disease (progressive motor neuronopathy/pmn). Pmn/pmn mice lose motoneurons and myelinated axons, and die at 6 weeks of age. When these mice were crossed with transgenic mice that overexpress human Bcl-2, there was a rescue of the facial motoneurons with a concomitant restoration of their normal soma size and expression of choline acetyltransferase. However, Bcl-2 overexpression did not prevent degeneration of myelinated axons in the facial and phrenic motor nerves and it did not increase the life span of the animals. Since Bcl-2 acts strictly on neuronal cell body survival without compensating for nerve degeneration in pmn/pmn/bcl-2 mice, this proto-oncogene would not in itself be sufficient for treatment of neurodegenerative diseases where axonal impairment is a major component.

Ultrastrutitural Pathology of an Inherited Lower Motor Neuron Disease of Pigs

The ultrastructural features of a recently described inherited lower motor neuron disease were studied in 5 affected pigs. Clinical signs comprised progressive ataxia and paresis of variable severity. Affected pigs, 6, 7, 15, 15, and 19 weeks of age, and 2 unrelated healthy pigs, 9 and 15 weeks of age, were anesthetized and their tissues were fixed by whole body perfusion with mixed aldehydes. From 1 or more affected pigs, samples of cervical and lumbar spinal ventral horn, lateral and ventral spinal columns, dorsal and ventral lumbar spinal nerve roots, 2 peripheral nerves (Nn. phrenicus and fibularis communis), and 2 skeletal muscles (Mm. diaphragma and tibialis cranialis) were examined ultrastructurally. There was widespread degeneration of myelinated axons in peripheral nerves and in lateral and ventral columns of lumbar and cervical segments of spinal cord. Axonal degeneration was present in ventral spinal nerve roots and was absent in dorsal spinal nerve roots sampled at the same lumbar levels. Unmyelinated axons in peripheral nerves and spinal nerve roots were unaffected. In 4 of 5 affected pigs, there were atrophic alpha motor neurons in cervical spinal cord that contained dense, round osmiophilic perikaryal inclusions up to 4 microns in diameter and round swollen mitochondria. Axonal regeneration was present in N. phrenicus of the 19-week-old affected pig that had clinical signs of longest duration (10 weeks). There was no morphologic evidence of axonal degeneration or spinal neuronal atrophy in either control pig. The ultrastructural features of this motor neuron disease distinguish it from other reported progressive spinal neuropathies of pigs.

The effects of aging on area 46 of the frontal cortex of the rhesus monkey.

An examination of cortex of area 46 in the floor of the principal sulcus in the frontal lobe of the rhesus monkey has been carried out using three young (4-6 years of age), one middle-aged (12 years of age), and five old (25-32 years of age) rhesus monkeys. Light microscopic examination revealed no age-related change in the thickness of the cortex, and no changes in the frequency of profiles of neurons displaying nuclei and contained in 250-micron-wide strips of 1-micron-thick sections. Since the diameters of the nuclei of the neurons were found to be the same in the young and old monkeys, it was concluded that there was no change in the numbers of neurons beneath similar areas of cortical surface of area 46 with age. This conclusion was reinforced by an electron microscopic examination, since there was no suggestion of degeneration of the cell bodies of the neurons, which accumulated but little lipofuscin in the old monkeys. However, there were signs of degeneration in some of the dendrites in the upper layers of the cortex in the old monkeys, especially in layer 1, in which many of the dendrites had lost organelles from their cytoplasm. The other notable change was a degeneration of myelinated axons in the deep layers and white matter in some of the old monkeys. In contrast to the neurons, the effects of aging on the neuroglial cells and pericytes were very obvious, since in the old monkeys each type of neuroglial cell accumulated large inclusions within its cytoplasm. Prior to fixation, these monkeys had been behaviorally tested using a series of spatial and visual recognition tasks, which revealed that relative to the young monkeys, the old monkeys as a group displayed memory impairment. On one task, the extent of the impairment for each old monkey correlated well with the extent of degeneration of myelinated fibers in the cortex and white matter. Consequently, it is suggested that age-related cognitive changes are unlikely to be a result of a loss of neurons, but might be due to an alteration in connections between the cortex and other brain structures.

The neurotrophic analogue of ACTH(4-9), Org 2766, protects against experimental allergic neuritis.

Demyelinating diseases such as multiple sclerosis or the Guillain-Barré syndrome originate from an autoimmune response resulting in the degradation of myelin and impaired neuronal function. Prophylactic administration of the neurotrophic peptide, H-Met(O2)-Glu-His-Phe-D-Lys-Phe-OH [an ACTH(4-9) analogue], to rats with experimental allergic neuritis, a model for the Guillain-Barré syndrome, markedly suppresses the clinical symptoms, protects against loss of motor coordination and prevents the degeneration of myelinated axons in the affected peripheral nerve. Therefore, this peptide may provide a new approach to the therapy of peripheral demyelinating polyneuropathies.

An experimental painful peripheral neuropathy due to nerve constriction: I. Axonal pathology in the sciatic nerve

A constriction injury to the sciatic nerve of the rat produces a painful peripheral neuropathy that is similar to the conditions seen in man. The pathology of the sciatic nerve in these animals was examined at 10 days postinjury, when the abnormal pain sensations are near maximal severity. The nerves were examined with (1) complete series of silver-stained longitudinal sections of pieces of the nerve (3 cm or more) that contained the constriction injury in the center, (2) toluidine blue-stained semithin sections taken at least 1 cm proximal and 1 cm distal to the constriction, and (3) EM sections taken adjacent to those stained with toluidine blue. One centimeter or more proximal to the constriction, both myelinated and unmyelinated axons were all normal. Nearer to the constriction, extensive degeneration of myelinated axons became increasingly common, as did signs of endoneurial edema. Distal to the constriction, the nerve was uniformly edematous and full of myelinic degeneration. There was a profound loss of large myelinated axons and a distinctly less severe loss of small myelinated and unmyelinated axons. These observations show that at 10 days postinjury the constriction produces a partial and differential deafferentation of the sciatic nerve's territory. The absence of degeneration in the nerve 1 cm proximal to the constriction indicates the survival of the primary afferent neurons whose axons are interrupted.

POEMS Syndrome: Ultrastructural Observations on the Sural Nerve

POEMS is an acronym that stands for a multisystem disorder that includes progressive sensorimotor Polyneuropathy, Organomegaly, Endocrinopathy, an M component in blood and/or concentrated urine, and Skin changes. The morphology of the peripheral nerves was mentioned in some of these cases and ranged from normal to those with segmental demyelination and/or degeneration of myelinated axons. We analyzed quantitatively the sural nerves of two cases of POEMS syndrome. Both nerves showed a severe loss of myelinated fibers, with a minor degree of regeneration. Degeneration of unmyelinated axons was observed, but to a lesser degree. There was marked collagen deposition in the endoneurium. The pathogenesis of the changes in the peripheral nerves and other organs in POEMS syndrome is still to be elucidated.

Spontaneous recovery from the encephalomyelitis in mice caused by street rabies virus.

Recovery from rabies was studied in an experimental model. Young adult mice were inoculated in a hindlimb footpad with street rabies virus (fox salivary gland isolate). In a group of 62 mice, 97% developed clinical rabies with paresis of the extremities and spasticity, and 37% recovered with neurological sequelae. There was an acute inflammatory reaction in the brainstem and grey matter of the spinal cord, and degeneration of myelinated axons in the white matter of the cord and in the dorsal roots. Rabies virus antigen was found in the central nervous system of all mice examined between day 5 and 13, and also in trigeminal and dorsal root ganglia. Surviving mice had neutralizing antibodies in serum and brain tissue, and 90% survived an intracerebral challenge with the CVS strain of fixed rabies virus. Spontaneous recovery from rabies encephalomyelitis was demonstrated with evidence of viral replication and pathological changes in the central nervous system.

Effects of aging on the neurons within area 17 of rhesus monkey cerebral cortex.

A light and electron microscopic examination of area 17 of the visual cortex in well-fixed young (5-6 years) and old (25-35 years) rhesus monkeys was carried out to determine the effects of age on neurons. The analyses were made in a portion of area 17 on the lateral surface of the hemisphere just caudal to the lunate sulcus. Light microscopic measurements of the mean cortical depth in vertically oriented 1-micron-thick sections reveal no obvious thinning with age, and the mean diameters of neuronal nuclei do not change with age. On the basis of counts of neuronal profiles containing nuclei in 250-microns-wide strips of 1-micron-thick sections passing through the entire depth of the cortex, no significant neuronal loss could be detected. These findings are consistent with our electron microscopic observations on this area of the cortex, for in the old monkeys the neurons show little cytological evidence of advanced age beyond the presence of a few lipofuscin granules, although the neuropil contains some profiles of degenerating small-caliber dendrites, myelinated axons, and a few axon terminals. Large vacuoles, some 10 microns or more in diameter, are present in the neuropil of the old animals. Some of these vacuoles appear to represent a late stage in the degeneration of myelinated axons, for they are bounded by a thin, laminated sheath. Other large vacuoles, of unknown origin, often contain membranous debris and have an attenuated limiting membrane. It is concluded that the cell bodies of neurons in area 17 of old rhesus monkeys do not show significant structural changes due to age, although some of the neuronal processes in the neuropil are affected.