Neuroscience
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There are two ways to picture white matter: as a grid of electrical wires or a network of roads. The first metaphor captures the classical function of an axon as conductor of action potentials (and information) from one brain region to another. The second one points to the important role of axons in a bi-directional transport of biological molecules and organelles between the cell body and synapse. ⋯ We then provide examples of key features of maturation and aging of white matter, as well as some of the common abnormalities observed in neurodevelopmental and neurodegenerative disorders. Next, we review work that motivated our focus on axonal diameter, and explain the relationships between transport and cytoskeleton within the axon. We will conclude by describing molecular machinery of axonal transport and genes that may contribute to inter-individual variations in axonal diameter and axonal transport.
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Studying how the healthy human brain develops is important to understand early pathological mechanisms and to assess the influence of fetal or perinatal events on later life. Brain development relies on complex and intermingled mechanisms especially during gestation and first post-natal months, with intense interactions between genetic, epigenetic and environmental factors. ⋯ Two main processes of early white matter development are reviewed: (1) establishment of connections between brain regions within functional networks, leading to adult-like organization during the last trimester of gestation, (2) maturation (myelination) of these connections during infancy to provide efficient transfers of information. Current knowledge from post-mortem descriptions and in vivo MRI studies is summed up, focusing on T1- and T2-weighted imaging, diffusion tensor imaging, and quantitative mapping of T1/T2 relaxation times, myelin water fraction and magnetization transfer ratio.
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Alterations in cerebrovascular structure and function may underlie the most common age-associated cognitive, psychiatric, and neurological conditions presented by older adults. Although much remains to understand, existing research suggests several age-associated detrimental conditions may be mediated through sometimes subtle small vessel-induced damage to the cerebral white matter. Here we review a selected portion of the vast work that demonstrates links between changes in vascular and neural health as a function of advancing age, and how even changes in low-to-moderate risk individuals, potentially beginning early in the adult age-span, may have an important impact on functional status in late life.
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Review Historical Article
The challenge of understanding cerebral white matter injury in the premature infant.
White matter injury in the premature infant leads to motor and more commonly behavioral and cognitive problems that are a tremendous burden to society. While there has been much progress in understanding unique vulnerabilities of developing oligodendrocytes over the past 30years, there remain no proven therapies for the premature infant beyond supportive care. ⋯ There has been an emphasis on hypoxia-ischemia and infection/inflammation as upstream etiologies, but less consideration of other contributory factors. This review highlights the evolution of white matter pathology in the premature infant, discusses the prevailing proposed etiologies, critically analyzes a sampling of common animal models and provides detailed support for our hypothesis that nutritional and hormonal deprivation may be additional factors playing critical and overlooked roles in white matter pathology in the premature infant.
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Alzheimer's disease (AD) has traditionally been regarded as a disease of the gray matter (GM). However, the advent of diffusion tensor imaging (DTI) has contributed to new knowledge about how changes in white matter (WM) microstructure in vivo may be directly related to the pathophysiology of AD. It is now evident that WM is heavily affected in AD, even at early stages. ⋯ Further, recent research has demonstrated relationships between increased cerebrospinal fluid levels of Tau proteins and changes in WM microstructure indexed by DTI, which could indicate that WM degeneration in pre-AD stages is related to ongoing axonal damage. We conclude that DTI is a promising biomarker for AD, with the potential also to identify subgroups of patients with especially high degree of WM affection, thereby contributing to more differentiated pre-AD diagnoses. However, more research and validation studies are needed before it is realistic to use this information in clinical practice with individual patients.