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

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.

Schizophrenia and the brain: a prospective clinico-neuropathological study

SynopsisThe neuropathological results from a prospective, systematically assessed, series of 56 schizophrenic patients and 56 age- and sex-matched normal controls have been presented.When compared with the normal controls, the brains of the schizophrenic subjects showed a significant reduction in brain weight and brain length with a concomitant increase in ventricular size. (All findings relate to measurements made after formalin fixation). In addition, the brains of the schizophrenic patients contained significantly more non-specific focal pathology and fibrillary gliosis than the controls.After exclusion of cases with moderate and severe Alzheimer-type change, cerebro-vascular disease and all forms of focal pathology, the structural brain changes (i.e. decrease in brain weight and brain length) continued to distinguish the schizophrenia group from the controls. Furthermore, an analysis of the clinical data showed that the structural brain changes were correlated in the schizophrenic patients with a measurement of pre-morbid function.The findings and their possible aetiological implications have been discussed.