Abstract WP107: Molecular Disorganization of Axons Adjacent to Human Cortical Microinfarcts

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Introduction: Ischemic brain lesions are pathologic hallmarks commonly associated with cognitive and cerebrovascular diseases. In particular, cortical microinfarcts are described as microscopically identified wedge shaped ischemic lesions such as cavitations with few remaining macrophages and fibrillary gliosis. These microscopic lesions are observed with high resolution magnetic resonance imaging in aging brains and in patients with cerebrovascular disease (CVD). Recent studies have suggested that strategically located microinfarcts strongly correlate with cognitive deficits, which can contribute to Alzheimer’s Disease (AD) as well as other forms of dementia.

Hypothesis: We have recently shown that there is altered axonal molecular organization in white matter areas adjacent to white matter lacunar and microinfarcts. In this study, we hypothesized that similar changes were present in nodal, paranodal, and axon initial segments adjacent to human cortical microinfarcts.

Methods: Paraffin-embedded sections of autopsy brain tissue from five patients (post mortem interval range= 4 to 45 h) with cortical microinfarcts reported in their clinical neuropathological examination were immunofluorescently labeled for nodal and paranodal markers including beta-IV spectrin, ankyrin-G, and contactin-associated protein (caspr). High magnification images were generated using confocal microscopy.

Results: Cases ranged in age from 73 to 93 years old. Comorbid neuropathologic diagnoses included AD (n=3) and mixed dementia (n=2). Adjacent to cortical microinfarcts, we observed significant elongation of paranodal segments and shortened axon initial segments adjacent to cortical microinfarcts. In adjacent cortical regions without microinfarcts, paranodal segments were less frequently abnormal and axon initial segment length appeared normal.

Conclusions: These data indicate that the molecular organization of axons adjacent to human cortical microinfarcts is abnormal providing support for a microinfarct penumbral injury that worsens the effect of these tiny strokes.

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