EXPRESSION OF INSULIN-LIKE GROWTH-FACTOR-I (IGF-1) AND IGF-BINDING PROTEIN-2 (IGF-BP2) IN THE HIPPOCAMPUS FOLLOWING CYTOTOXIC LESION OF THEDENTATE GYRUS

Receptor binding and gene expression of several members of the IGF gen e family were examined in the rat brain following lesion of the hippoc ampal dentate gyrus granular cells by intradentate colchicine injectio n. Dentate granular cell loss was accompanied by extensive reactive gl iosis in the lesioned hippocampus and damaged overlying cortex, as ver ified by the increase in GFAP mRNA and BS-P lectin binding. At 4 days post-lesion, I-125-IGF-2 binding was dramatically increased within the lesioned dentate gyrus and damaged overlying cortex, and corresponded temporally and anatomically with increased IGF-BP2 gene expression fo llowing the lesion. Increased IGF-BP3 gene expression was only observe d in the overlying cortex at 10 days post-lesion, and corresponded wit h an increase in I-125-IGF-1 binding at the injured surface of the cor tex. Type-2 IGF receptor mRNA expression was reduced to background lev els in the lesioned dentate gyrus, suggesting that IGF-BP2 was a major component of the observed increase in I-125-IGF-2 binding. In situ hy bridization also revealed a prominent increase in IGF-L mRNA expressio n by 4 days post-lesion, which was localized within the lesioned denta te gyrus and damaged cortical areas, and was shown to be expressed by microglia. While no IGF-S mRNA expression was observed within the CNS, either prior to, or following the lesion, IGF-2 mRNA expression was o bserved in the choroid plexus, meningeal membranes, and in blood vesse l endothelium, providing a potential source for the transport of IGF-2 into the CNS. In the injured CNS, increased IGF-BP2 expression may ac t to maintain or transport IGF-1 or IGF-2, as well as modulate the loc al autocrine and paracrine actions of the IGFs. Increased microglial I GF-1 expression following colchicine treatment con elates with the tim ing of a number of post-traumatic post-traumatic events within the CNS , suggesting that IGF-1 may have a role as a neuroprotectant for survi ving neurons and signal for local neuronal sprouting, as well as a rol e in reactive astrogliosis. (C) 1996 Wiley-Liss, Inc.