Experimental approaches to white matter disease

The study of the cerebral white matter (WM) in experimental models of hypoxia and ischemia has been for a long time neglected, the interest of investigators being focused on the response of the neuronal population. The increasing frequency with which modern neuroimaging techniques disclose alterations of the WM of possibly vascular origin has called some attention to other components of the cerebral parenchyma, namely oligodendrocytes and myelinated axons. The studies here reviewed show that it is possible to investigate the WM alterations in appropriate models of cerebral ischemia. In rodents, chronic ischemia produces extracellular fluid accumulation in the WM, moderate loss of oligodendroglial cells and reactive astrogliosis, all of which contribute to the rarefied appearance under the light microscope. These changes are similar to those found in many patients with leukoencephalopathy of possibly vascular origin. The results of experiments using a rat model of focal brain ischemia show that oligodendrocytes and myelinated fibers are extremely sensitive to ischemic insults with alterations of the subcortical WM detected at a very early time. Opportune modifications of these animal models may represent a valuable source of information on the pathogenesis and pathophysiology of human vascular disease of the WM.