Apoptosis in leukoaraiosis lesions

Abstract

Leukoaraiosis (LA), an age-related degenerative condition, appears as an area of hyperintense signal in the deep white matter on MRI. It may be caused by chronic ischemia. LA lesions are characterized by demyelination, loss of glial cells, spongy appearance, and occlusion of veins and venules by collagenous thickening of the vessel walls. Since necrosis is not obvious in LA lesions, we investigated the occurrence of apoptosis. We obtained 1.5-cm-thick coronal brain slices at autopsy from two patients with LA. MRI was performed on the brain slices. Blocks were fixed in formalin, embedded in paraffin, and sectioned. Sections were stained by several methods including the TUNEL method for DNA fragmentation. Some TUNEL-positive cells showed nuclear morphology indicative of apoptosis. In case 1, TUNEL-positive cells were more numerous in an LA lesion than in nearby unaffected white matter ( P=0.008). In case 2, LA lesions were examined in six areas; left and right frontal, middle, and occipital slices. TUNEL-positive cells were more numerous in the LA lesions than in nearby white matter ( P=0.002). We also found TUNEL-positive cells in the cortex and in the walls of blood vessels. In case 1, more severe venous collagenosis was found in the LA lesion, which was near the cortex, than in the periventricular area, where venous collagenosis and LA are more commonly found. The presence of numerous scattered cells in the LA lesions showing DNA fragmentation suggests that those cells are damaged and dying, at least some by apoptosis. The apoptosis in the white matter adjacent to the LA lesions suggests progressive cell loss and expansion of the LA lesions.