TRANSFORMING GROWTH-FACTOR-BETA-1 AND FIBRONECTIN MESSENGER-RNA IN RAT-BRAIN - RESPONSES TO INJURY AND CELL-TYPE LOCALIZATION

Transforming growth factor-beta1 rapidly increases in adult rat brain in response to experimental lesions. This study characterized the sche dule of changes, regional distribution, and cellular localization of s triatal transforming growth factor-beta1 messenger RNA and fibronectin messenger RNA following partial striatal deafferentation by frontal c ortex ablation. Frontal cortex ablation induced striatal transforming growth factor-beta1 messenger RNA elevations that coincided temporally and overlapped anatomically with the course of degeneration of cortic o-striatal afferent fibers. Within three days post-lesioning, transfor ming growth factor-beta1 messenger RNA was localized at the cortical w ound. By 10 days, the anatomical site of transforming growth factor-be ta1 messenger RNA expression shifted to the dorsal half of the deaffer ented striatum and co-localized with OX-42+ immunostained microglia-ma crophage at the site of degenerating afferent terminals, Similarly, fi bronectin messenger RNA also shifted from the cortical wound to the de afferented striatum by 10 days post-lesioning. Fibronectin messenger R NA was localized to glial fibrillary acidic protein+ immunostained ast rocytes surrounding degenerating corticostriatal afferents. Infusion o f transforming growth factor-beta1 peptide elevated striatal and corti cal fibronectin messenger RNA. These findings suggest that microglia-m acrophage associated with degenerating afferent fibres can upregulate transforming growth factor-beta1 messenger RNA and may influence fibro nectin messenger RNA synthesis in reactive astrocytes. This study sugg ests that transforming growth factor-beta1 has a role in controlling e xtracellular matrix synthesis following brain injury, which is analogo us to that in peripheral wound healing.