Transforming growth factor β1 and fibronectin messenger RNA in rat brain: Responses to injury and cell-type localization

Abstract

Transforming growth factor-β1 rapidly increases in adult rat brain in response to experimental lesions. This study characterized the schedule of changes, regional distribution, and cellular localization of striatal transforming growth factor-β1 messenger RNA and fibronectin messenger RNA following partial striatal deafferentation by frontal cortex ablation. Frontal cortex ablation induced striatal transforming growth factor-β1 messenger RNA elevations that coincided temporally and overlapped anatomically with the course of degeneration of cortico-striatal afferent fibers. Within three days post-lesioning, transforming growth factor-β1 messenger RNA was localized at the cortical wound. By 10 days, the anatomical site of transforming growth factor-β1 messenger RNA expression shifted to the dorsal half of the deafferented striatum and co-localized with OX-42 + immunostained microgliamacrophage at the site of degenerating afferent terminals. Similarly, fibronectin messenger RNA also shifted from the cortical wound to the deafferented striatum by 10 days post-lesioning. Fibronectin messenger RNA was localized to glial fibrillary acidic protein + immunostained astrocytes surrounding degenerating corticostriatal afferents. Infusion of transforming growth factor-β1 peptide elevated striatal and cortical fibronectin messenger RNA. These findings suggest that microglia-macrophage associated with degenerating afferent fibres can upregulate transforming growth factor-β1 messenger RNA and may influence fibronectin messenger RNA synthesis in reactive astrocytes. This study suggests that transforming growth factor-β1 has a role in controlling extracellular matrix synthesis following brain injury, which is analogous to that in peripheral wound healing.