Abstract 86: Expanding The Lacunar Infarct: Molecular Reorganization Of Axons Adjacent To Human White Matter Stroke
White matter stroke compromises approximately 25% of all strokes and accounts for significant disability by directly damaging myelin and axons. Patients presenting with white matter stroke often worsen clinically during the acute presentation. MRI studies demonstrate that white matter stroke lesions often expand in size over time. In part, this may be due to progressive expansion of infarcts through functional disruption of adjacent axons. The function of myelinated axons is dependent on molecular clustering of voltage-gated sodium channels at nodes of Ranvier. This clustering is partly dependent on the interaction with myelinating oligodendrocytes at axonal regions adjacent to nodes, termed paranodes. Here, we examined 10 autopsy cases of patients with lacunar infarcts and 3 controls for the molecular integrity of axonal microdomains adjacent to stroke. Lacunar infarcts were identified using clinical history and H&E sections. Serial sections were labeled for immunofluorescent markers of nodes and paranodes as well as neurofilaments and myelin basic protein. Compared to controls, there is lengthening of paranodes adjacent to white matter stroke consistent with disrupted axon-oligodendrocyte molecular interactions. In addition, immunolabeling for both voltage-gated sodium channels and their cytoskeletal anchors are disrupted in peri-infarct tissue. These abnormalities of axonal microdomains are present in a region larger than the infarct size as measured by H&E. These results indicate that white matter stroke produces functional disorganization of axons adjacent to the traditional lacune. A white matter stroke peri-infarct marked by molecularly disorganized axons provides a new therapeutic target for the treatment of white matter stroke.
- © 2012 by American Heart Association, Inc.