Multipe Sclerosis - Pathology

Axonal Injury -

Axonal injury in multiple sclerosis

Curr Neurol Neurosci Rep. 2003 May;3(3):231-7.

Rammohan KW.

The pivotal role of axons in the pathophysiology and pathogenesis of multiple sclerosis (MS) is increasingly becoming the focus of our attention. Axonal injury, considered at one time to be a late phenomenon, is now recognized as an early occurrence in the inflammatory lesions of MS. There is converging evidence from histopathologic, as well as magnetic resonance imaging and magnetic resonance spectroscopy studies, that axons play a crucial and dynamic role during the evolution of MS pathology and the development of clinical disability. It has been repeatedly demonstrated that neurologic functional impairment correlates best with axonal, rather than myelin, injury. The pathophysiology of axonal injury remains speculative. Although generally considered to be sequelae of demyelination, it is possible that axonal injury in MS is indeed a primary event. The discovery that axonal injury can be reversible has provided an impetus to institute early therapy. The finding that irreversible axonal transection occurs in early lesions has underscored now, more than ever before, the need to curtail inflammation and the need to institute early treatment with disease-modifying agents. The axon will undoubtedly remain the focus of our attention regarding research on MS now and in the future.

Publication Types:

• Review

Axonal damage in multiple sclerosis

Neurol Neurochir Pol. 2002 May-Jun;36(3):505-12.

Bartosik-Psujek H, Stelmasiak Z.

Traditionally, it was believed in MS, that axonal loss occurred in chronic lesions. However, new findings suggest that axonal transection can begin very early in the course of multiple sclerosis and axonal damage was found in active and chronic active MS lesions, particularly in areas of acute inflammation and demyelination. The mechanisms of axonal loss are uncertain, but may involve axonal degeneration secondary to demyelination, the action of inflammatory mediators and immune attack directed at axonal components. Axonal destruction and it's progression, is the major cause of irreversible damage in the CNS and the increase of disability in MS patients. Currently, new diagnostic methods (MRI, MR spectroscopy, magnetic transfer, histopathological and biochemical study) allow better to know the mechanisms of neuronal damage.

Publication Types:

• Review

Axonal degeneration in multiple sclerosis: the mitochondrial hypothesis

Curr Neurol Neurosci Rep. 2009 Sep;9(5):411-7. /p>

Su KG, Banker G, Bourdette D, Forte M.

Multiple sclerosis (MS) is a chronic disease of the central nervous system, affecting more than 2 million people worldwide. Traditionally considered an inflammatory demyelinating disease, recent evidence now points to axonal degeneration as crucial to the development of irreversible disability. Studies show that axonal degeneration occurs throughout the entire course of MS. Although the specific mechanisms causing axonal damage may differ at various stages, mitochondrial failure seems to be a common underlying theme. This review addresses the mitochondrial hypothesis for axonal degeneration in MS, highlighting the mechanisms by which mitochondrial dysfunction leads to axonal disruption in acute inflammatory lesions and the chronic axonopathy in progressive MS. Emphasis is placed on Ca(2+), free radical production, and permeability transition pore opening as key players in mitochondrial failure, axonal transport impairment, and subsequent axonal degeneration. In addition, the role of mitochondria as therapeutic targets for neuroprotection in MS is addressed.

Publication Types:

• Review

Publication Types:

• Review