LESIONING OF THE INFERIOR OLIVE USING A VENTRAL SURGICAL APPROACH - CHARACTERIZATION OF TEMPORAL AND SPATIAL ASTROCYTIC RESPONSES AT THE LESION SITE AND IN CEREBELLUM

Activated astrocytes, intrinsic components of both local and remote (a xonal target regions) central nervous system injury responses, are now recognized as active metabolic and regulatory mediators in many neuro logical disorders. To further define these responses, we devised a new ventral surgical approach to unilaterally lesion the inferior olivary nuclear complex, which has a single predominant remote target, the ce rebellum. Activated astrocyte number, volume, and density, as well as the total volume of brainstem involved in the astrocytic response, all peaked at postlesion day (pld) 4, returning toward, but not to, unope rated control values at pld 24 (p < 0.05). In contrast, the peak astro cyte response in the cerebellum was delayed, being greatest at pld 6 ( p < 0.05 compared to control or pld 2). These responses were associate d with increases in overexpression of S100 beta, an astrocyte-derived neurite growth factor, and with an increase in cerebellar steady-state levels of a neuronal injury response protein, the beta-amyloid precur sor protein (beta-APP), This is similar to correlated increases in the se two proteins that are found in epilepsy and Alzheimer disease, Our studies defining remote astrocytic and neuronal responses may be impor tant for understanding glial-neuronal mechanisms underlying the spread of neuropathological changes in conditions such as Alzheimer disease.