Localization of transforming growth factor-beta 1 and receptor mRNA after experimental spinal cord injury

Transforming growth factor-beta 1 (TGF beta 1) is a cytokine/growth factor found within the pathological central nervous system. TGF beta 1 has been s hown to inhibit the release of cytotoxic molecules from microglia and macro phages, decrease astrocyte proliferation, and promote neuron survival. Beca use of the relevance of these actions to spinal cord injury, we examined TG F beta 1 and its receptors beta RI and beta RII mRNA levels and localizatio n within the contused rat spinal cord using in situ hybridization. At the l esion site, TGF beta 1 mRNA peaked at 7 days postinjury and declined therea fter. Temporal and spatial localization of the beta RI and beta RII recepto r mRNA closely mimicked that for TGF beta 1 in the epicenter. TGF beta 1, b eta RI, and beta RII mRNAs also were elevated rostral and caudal to the inj ury, especially in regions known to contain activated microglia and degener ating axon profiles. Immunohistochemical staining of nearby sections confir med that the highest levels of TGF beta 1 and receptor mRNA corresponded to regions filled with activated microglia and macrophages. The similar expre ssion pattern of TGP beta 1, beta RI, and beta RII mRNA within the injured spinal cord suggests a local site of action. Since TGF beta 1 can act as an immunosuppressant as well as a stimulant for growth factors and neurite sp routing, it likely plays an important role, both temporally and spatially, in orchestrating postinjury events within the spinal cord. (C) 2000 Academi c Press.