Chronic white matter microvascular ischemic disease

White matter stroke secondary to microvascular injury is common yet the molecular changes that accompany ischemic damage to white matter are poorly understood. MRI imaging studies suggest that abnormalities exist within the white matter adjacent to lacunar infarcts and this may lead to infarct progression through a functional disruption of adjacent axons. Hereditary subcortical stroke syndromes provide a unique opportunity to study the molecular mechanisms of cerebral microvascular disease and its effect on white matter. Here, we examined two autopsy cases of hereditary endotheliopathy with retinopathy, nephropathy and stroke (HERNS) syndrome with severe microvascular ischemic disease in the cerebral white matter to determine the molecular organization of myelin and axons within the cerebral white matter adjacent to lacunar infarcts in these patients. MRI imaging was used to identify regions of prior lacunar infarction or FLAIR hyperintensity. Serial paraffin-embedded sections within these regions were immunolabeled for markers of nodes of Ranvier and paranodes as well as neurofilaments and myelin basic protein and compared to normal-appearing white matter and non-diseased controls. Compared to controls, HERNS cases demonstrate lengthening of paranodes and disrupted nodal staining patterns consistent with a loss of normal axon-oligodendrocyte molecular interactions. These abnormalities of axonal microdomains are present beyond the region of infarction suggested by MRI and H&E sections and occur in areas of FLAIR hyperintensity without frank lacunar infarction. These results indicate there is a peri-infarct in white matter stroke marked by molecular disruption of axons surrounding the infarct that may serve as a new therapeutic target for this currently untreatable form of ischemic stroke.

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A Taxonomy of Brain–Behavior Relationships After Stroke

Journal of Speech Language and Hearing Research ◽

10.1044/2019_jslhr-l-rsnp-19-0032 ◽

2019 ◽

Vol 62 (11) ◽

pp. 3907-3922 ◽

Cited By ~ 3

Author(s):

Peter E. Turkeltaub

Keyword(s):

White Matter ◽

Brain Tissue ◽

Cognitive Abilities ◽

Behavioral Outcomes ◽

Brain Regions ◽

Cognitive Outcomes ◽

Future Research ◽

Ischemic Disease ◽

Brain Behavior ◽

The Brain

Purpose Understanding the brain basis of language and cognitive outcomes is a major goal of aphasia research. Prior studies have not often considered the many ways that brain features can relate to behavioral outcomes or the mechanisms underlying these relationships. The purpose of this review article is to provide a new framework for understanding the ways that brain features may relate to language and cognitive outcomes from stroke. Method Brain–behavior relationships that may be important for aphasia outcomes are organized into a taxonomy, including features of the lesion and features of brain tissue spared by the lesion. Features of spared brain tissue are categorized into those that change after stroke and those that do not. Features that change are further subdivided, and multiple mechanisms of brain change after stroke are discussed. Results Features of the stroke, including size, location, and white matter damage, relate to many behavioral outcomes and likely account for most of the variance in outcomes. Features of the spared brain tissue that are unchanged by stroke, such as prior ischemic disease in the white matter, contribute to outcomes. Many different neurobiological and behavioral mechanisms may drive changes in the brain after stroke in association with behavioral recovery. Changes primarily driven by neurobiology are likely to occur in brain regions with a systematic relationship to the stroke distribution. Changes primarily driven by behavior are likely to occur in brain networks related to the behavior driving the change. Conclusions Organizing the various hypothesized brain–behavior relationships according to this framework and considering the mechanisms that drive these relationships may help investigators develop specific experimental designs and more complete statistical models to explain language and cognitive abilities after stroke. Eight main recommendations for future research are provided. Presentation Video https://doi.org/10.23641/asha.10257578

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Review for "The distribution, number and certain neurochemical identities of infracortical white matter neurons in the brains of three megachiropteran bat species"

10.1002/cne.24894/v1/review2 ◽

2020 ◽

Keyword(s):

White Matter

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FT-IR microspectroscopic analysis of diseased white matter brain tissues

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100141214 ◽

1995 ◽

Vol 53 ◽

pp. 968-969

Author(s):

Steven M. Le Vine ◽

David L. Wetzel

Keyword(s):

White Matter ◽

Gray Matter ◽

Twitcher Mouse ◽

Grid Pattern ◽

Marked Contrast ◽

Spatially Resolved ◽

Ft Ir ◽

Ir Microspectroscopy ◽

Chemical Evidence

In situ FT-IR microspectroscopy has allowed spatially resolved interrogation of different parts of brain tissue. In previous work the spectrrscopic features of normal barin tissue were characterized. The white matter, gray matter and basal ganglia were mapped from appropriate peak area measurements from spectra obtained in a grid pattern. Bands prevalent in white matter were mostly associated with the lipid. These included 2927 and 1469 cm-1 due to CH2 as well as carbonyl at 1740 cm-1. Also 1235 and 1085 cm-1 due to phospholipid and galactocerebroside, respectively (Figs 1and2). Localized chemical changes in the white matter as a result of white matter diseases have been studied. This involved the documentation of localized chemical evidence of demyelination in shiverer mice in which the spectra of white matter lacked the marked contrast between it and gray matter exhibited in the white matter of normal mice (Fig. 3).The twitcher mouse, a model of Krabbe’s desease, was also studied. The purpose in this case was to look for a localized build-up of psychosine in the white matter caused by deficiencies in the enzyme responsible for its breakdown under normal conditions.

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