Expression of growth inhibitory factor (metallothionein-III) mRNA and protein following excitotoxic immature brain injury.

The balance between trophic factors and inhibitory molecules is likely to determine the outcome of neural tissue damage. The growth inhibitory factor (GIF), a member of the metallothionein family of proteins named metallothionein-III (MT-III), has been suggested to play an important role in tissue repair after adult brain injury. Because no information is available on this factor in relation to immature brain damage, we examined the chronological changes of GIF (MT-III) mRNA and protein following excitotoxic lesions to the postnatal day 9 brain using in situ hybridization and immunocytochemical techniques. We observed a significant decrease of neuronal GIF (MT-III) mRNA and protein levels between 4 and 24 hours postinjury and an increase in glial GIF (MT-III) levels. Double immunocytochemical techniques showed GIF (MT-III) and GFAP positive astrocytes from 2-4 hours postinjury. From 3 days postinjury strongly reactive astrocytes expressed strong levels of both GIF (MT-III) mRNA and protein, which were maintained in the glial scar formed at longer times. These results show the expression of an inhibitory molecule by postnatal reactive astrocytes. Glial GIF (MT-III) expression may play an important role in the tissue reconstruction after immature brain damage.