Molecular disorganization of axons adjacent to @entity1 XXXX .

@entity1 @entity8 @entity64 @entity2610 @entity66 @entity303 @entity73 @entity16 @entity1188 @entity74 @entity989 @entity62 @entity528
UNASSIGNED: Cerebral @entity62 , resulting in @entity16 that ranges from @entity1188 to @entity62 seen on magnetic resonance imaging. These lesions are common and result in both @entity64 and accumulate over time, resulting in @entity73 and @entity303 . Magnetic resonance imaging studies suggest that these lesions progress over time, accumulate adjacent to prior lesions and have a penumbral region susceptible to further injury. The pathological correlates of this adjacent injury in surviving myelinated axons have not been previously defined. In this study, we sought to determine the molecular organization of axons in tissue adjacent to @entity1188 and in the regions surrounding microinfarcts, by determining critical elements in axonal function: the morphology and length of node of Ranvier segments and adjacent paranodal segments. We examined post-mortem brain tissue from six @entity1 with @entity1188 and tissue from two @entity1 with @entity989 and @entity62 (previously known as @entity74 with @entity989 , @entity8 and @entity64 ) who accumulate progressive @entity62 in the form of lacunar and microinfarcts. In axons adjacent to @entity1188 yet extending up to 150% of the @entity1188 diameter away, both nodal and paranodal length increase by    20% and 80%, respectively, reflecting a loss of normal cell-cell adhesion and signalling between axons and oligodendrocytes. Using premorbid magnetic resonance images, brain regions from @entity1 with @entity989 and @entity62 that harboured periventricular @entity62 were selected and the molecular organization of axons was determined within these regions. As in regions adjacent to @entity1188 , nodal and paranodal length in white matter of these @entity1 is increased. @entity2610 and neurofilament immunolabelling demonstrates that axons in these adjacent regions have preserved axonal cytoskeleton organization and are generally myelinated. This indicates that the loss of normal axonal microdomain architecture results from disrupted axoglial signalling in white matter adjacent to lacunar and microinfarcts. The loss of the normal molecular organization of nodes and paranodes is associated with @entity528 and may lead to impaired conduction velocity across surviving axons after @entity64 . These findings demonstrate that the degree of @entity62 associated with cerebral @entity66 extends well beyond what can be identified using imaging techniques and that an improved understanding of the neurobiology in these regions can drive new therapeutic strategies for this disease entity.
