Neuroepidemiology and Neuropathology of Periventricular White Matter Injury of the Premature Newborn
Periventricular white matter injury is the most important neuropathological substrate for the subsequent neurological disability, i.e., cerebral palsy and cognitive deficits, observed in premature infants. In 1973 Leviton and Gilles began a classic series of neuroepidemiologic and neuropathologic studies linking bacteriemia and endotoxin to the cause of this type of injury (J. Neurol. Sci., 1973; Ann. Neurol., 1984; J. Neurol. Sci., 1976; The Developing Brain: Growth and Epidemiologic Neuropathology, 1983). Subsequent work showed that ischemia also is crucial in pathogenesis of this injury. The work of Leviton and Gilles led to the later discovery of a link between periventricular white matter injury of prematurity and maternal infection, a very important cause of prematurity. These neuroepidemiologic and neuropathological investigations have proved to be the foundation for current cellular and molecular studies of the role of cytokines, reactive oxygen and nitrogen species and glutamate in oligodendroglial cell death, carried out especially in cell culture and in animal models (Volpe, Rosenberg, Jensen, Follett, Kinney and Vartanian). Leviton now leads a major multi-center, NIH-funded grant, based in this IDDRC that addresses the clinical and epidemiological correlates of periventricular white matter injury identified in the living premature infant by cranial ultrasonography. Landmark work of Dr. Hannah Kinney has shown that PVL is characterized by evidence for oxidative and nitrosative stress and by a remarkable infiltration with activated microglia. This research interfaces with a considerable amount of work in the current IDDRC in both the Clinical/Translational Neuroscience Program (Kinney, Volpe, and Jensen) and the Basic Neuroscience Program (Rosenberg, Volpe, Jensen and Vartanian).