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Myelin Degeneration (myelin + degeneration)

Distribution by Scientific Domains

Medical Sciences	60%

Selected Abstracts

The contribution of activated phagocytes and myelin degeneration to axonal retraction/dieback following spinal cord injury

EUROPEAN JOURNAL OF NEUROSCIENCE, Issue 8 2004
Lowell T. McPhail
Abstract Myelin-derived molecules inhibit axonal regeneration in the CNS. The Long,Evans Shaker rat is a naturally occurring dysmyelinated mutant, which although able to express the components of myelin lacks functional myelin in adulthood. Given that myelin breakdown exposes axons to molecules that are inhibitory to regeneration, we sought to determine whether injured dorsal column axons in a Shaker rat would exhibit a regenerative response absent in normally myelinated Long,Evans (control) rats. Although Shaker rat axons did not regenerate beyond the lesion, they remained at the caudal end of the crush site. Control rat axons, in contrast, retracted and died back from the edge of the crush. The absence of retraction/dieback in Shaker rats was associated with a reduced phagocytic reaction to dorsal column crush around the caudal edge of the lesion. Systemic injection of minocycline, a tetracycline derivative, in control rats reduced both the macrophage response and axonal retraction/dieback following dorsal column injury. In contrast, increasing macrophage activation by spinal injection of the yeast particulate zymosan had no effect on axonal retraction/dieback in Shaker rats. Schwann cell invasion was reduced in minocycline-treated control rats compared with untreated control rats, and was almost undetectable in Shaker rats, suggesting that like axonal retraction/dieback, spinal Schwann cell infiltration is dependent upon macrophage-mediated myelin degeneration. These results indicate that following spinal cord injury the phagocyte-mediated degeneration of myelin and subsequent exposure of inhibitory molecules to the injured axons contributes to their retraction/dieback. [source]

Cellular pathology in multiple system atrophy

NEUROPATHOLOGY, Issue 4 2006
Koichi Wakabayashi
Multiple system atrophy (MSA) is a sporadic, adult-onset neurodegenerative disease, which is characterized by striatonigral degeneration, olivopontocerebellar atrophy, and preganglionic autonomic lesions in any combination. The histological hallmark is the presence of argyrophilic fibrillary inclusions in the oligodendrocytes, referred to as glial cytoplasmic inclusions (GCIs). Fibrillary inclusions are also found in the neuronal somata, axons, and nucleus. Neuronal cytoplasmic inclusions are frequently found in the pontine and inferior olivary nuclei. Since the discovery of ,-synuclein as a major component of glial and neuronal inclusions in MSA, two neurodegenerative processes have been considered in this disease: one is due to the widespread occurrence of GCIs associated with oligodendroglia,myelin degeneration (oligodendrogliopathy) in the central nervous system, and the other is due to the filamentous aggregation of ,-synuclein in the neurons in several brain regions. These two degenerative processes might synergistically cause neuronal depletion in MSA. [source]

Role of n-type voltage-dependent calcium channels in autoimmune optic neuritis,

ANNALS OF NEUROLOGY, Issue 1 2009
Ivana Gadjanski PhD
Objective The aim of this study was to investigate the role of voltage-dependent calcium channels (VDCCs) in axon degeneration during autoimmune optic neuritis. Methods Calcium ion (Ca2+) influx into the optic nerve (ON) through VDCCs was investigated in a rat model of optic neuritis using manganese-enhanced magnetic resonance imaging and in vivo calcium imaging. After having identified the most relevant channel subtype (N-type VDCCs), we correlated immunohistochemistry of channel expression with ON histopathology. In the confirmatory part of this work, we performed a treatment study using ,-conotoxin GVIA, an N-type specific blocker. Results We observed that pathological Ca2+ influx into ONs during optic neuritis is mediated via N-type VDCCs. By analyzing the expression of VDCCs in the inflamed ONs, we detected an upregulation of ,1B, the pore-forming subunit of N-type VDCCs, in demyelinated axons. However, high expression levels were also found on macrophages/activated microglia, and lower levels were detected on astrocytes. The relevance of N-type VDCCs for inflammation-induced axonal degeneration and the severity of optic neuritis was corroborated by treatment with ,-conotoxin GVIA. This blocker led to decreased axon and myelin degeneration in the ONs together with a reduced number of macrophages/activated microglia. These protective effects were confirmed by analyzing the spinal cords of the same animals. Interpretation We conclude that N-type VDCCs play an important role in inflammation-induced axon degeneration via two mechanisms: First, they directly mediate toxic Ca2+ influx into the axons; and second, they contribute to macrophage/microglia function, thereby promoting secondary axonal damage. Ann Neurol 2009;66:81,93 [source]

Histological and Ultrastructural Analysis of White Matter Damage after Naturally-occurring Spinal Cord Injury

BRAIN PATHOLOGY, Issue 2 2006
Peter M. Smith
Detailed analysis of the structural changes that follow human clinical spinal cord injury is limited by difficulties in achieving adequate tissue fixation. This study bypasses this obstacle by examining the spinal cord from paraplegic domestic animals, enabling us to document the ultrastructural changes at different times following injury. In all but one case, injury resulted from a combination of contusion and compression. There was infarction and hemorrhage, followed by gray matter destruction and the rapid development of a variety of white matter changes including axon swelling and myelin degeneration. Axons greater than 5 µm in diameter were more susceptible to degenerative changes, whereas smaller axons, particularly those in the subpial region, were relatively well preserved. Demyelinated axons were seen within 2 weeks after injury and, at later time points, both Schwann cell and oligodendrocyte remyelination was common. More subtle white matter abnormalities were identified by examining sagittal sections, including focal accumulation of organelles in the axoplasm and partial and paranodal myelin abnormalities. These observations serve to validate observations from experimental models of spinal contusion but also highlight the complexity of naturally occurring (ie, clinical) spinal injury. They also raise the possibility that focal abnormalities such as paranodal demyelination may contribute to early axonal dysfunction and possibly to progressive tissue damage. [source]