DIFFERENTIAL NEURONAL AND ASTROCYTIC EXPRESSION OF TRANSFORMING GROWTH-FACTOR-BETA ISOFORMS IN RAT HIPPOCAMPUS FOLLOWING TRANSIENT FOREBRAIN ISCHEMIA

Although transforming growth factor-beta (TGF-beta) is known to be mul tifunctional in many physiological systems, its role in the brain is u ndergoing elucidation. The situation is made more complex by the prese nce of multiple isoforms, which may be differentially regulated and ha ve various activities in each particular cell type. Because neurons ar e dependent on neurotrophic factors for survival, we utilized a rat mo del of transient forebrain ischemia (TFI) to test the hypothesis that TGF-beta isoforms are important in the hippocampal response to injury. Northern blot analysis demonstrated a differential and temporal alter ation in TGF-beta isoform expression following TFI. Ln-situ hybridizat ion experiments revealed that at day 1 following TFI. there was a stro ng neuronal increase in the TGF beta-1 transcript but a reciprocal dec rease in TGF-beta 2 and -beta 3 transcript levels, Immunohistochemical analysis of all three TGF-beta s demonstrated at day 1 following TFI a loss of the immunoreactive proteins in the vulnerable CA-1 hippocamp al neurons, but protein preservation in the CA-2-4 neurons which are m ore resistant to the ischemic insult. At 3-5 days following TFI, signi ficant extraneuronal changes in TGF-beta isoform expression were also detected. Double-staining experiments with antibody to glial fibrillar y acidic protein (GFAP) as a marker for astrocytes, and lectin isolect in B4 Griffonia simplicifolia for microglia, demonstrated increased ex pression of all TGF-beta isoforms in astrocytes but not microglia. Tak en together, these results suggest thar the TGF-beta peptides in neuro ns and astrocytes are important endogenous mediators in the CNS respon se to ischemic injury.