Neuroscience
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The CNS white matter makes up about half of the human brain, and with advances in human imaging it is increasingly becoming clear that changes in the white matter play a major role in shaping human behavior and learning. However, the mechanisms underlying these white matter changes remain poorly understood. ⋯ Collaboration between fields is essential to understand the function of the white matter, but due to differences in methods and field-specific 'language', communication is often hindered. In this review, we try to address this hindrance by introducing the methods and providing a basic background to myelin biology and human imaging as a prelude to the other reviews within this special issue.
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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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About half of the human brain is white matter, characterized by axons covered in myelin, which facilitates the high speed of nerve signals from one brain area to another. At the time of myelination, the oligodendrocytes that synthesize myelin require a large amount of energy for this task. Conditions that deprive the tissue of energy can kill the oligodendrocytes. ⋯ In addition, lactate carries signals as a volume transmitter. Myelin thus seems to serve as a provider of substrates and signals for axons, and not as a mere insulator. We review the fluxes of lactate in white matter and their significance in brain function.
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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.
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Oligodendrocytes and the myelin they produce are a remarkable vertebrate specialization that enables rapid and efficient nerve conduction within the central nervous system. The generation of myelin during development involves a finely-tuned pathway of oligodendrocyte precursor specification, proliferation and migration followed by differentiation and the subsequent myelination of appropriate axons. ⋯ Many of these regulatory mechanisms have recurring roles in regulating several transitions during oligodendrocyte development, highlighting their importance. It is also highly likely that many of these developmental mechanisms will also be involved in myelin repair in human neurological disease.