Localization of transforming growth factor-β1 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 shown to inhibit the release of cytotoxic molecules from microglia and macrophages, decrease astrocyte proliferation, and promote neuron survival. Because of the relevance of these actions to spinal cord injury, we examined TGF beta 1 and its receptors beta RI and beta RII mRNA levels and localization within the contused rat spinal cord using in situ hybridization. At the lesion site, TGF beta 1 mRNA peaked at 7 days postinjury and declined thereafter. Temporal and spatial localization of the beta RI and beta RII receptor mRNA closely mimicked that for TGF beta 1 in the epicenter. TGF beta 1, beta RI, and beta RII mRNAs also were elevated rostral and caudal to the injury, especially in regions known to contain activated microglia and degenerating axon profiles. Immunohistochemical staining of nearby sections confirmed that the highest levels of TGF beta 1 and receptor mRNA corresponded to regions filled with activated microglia and macrophages. The similar expression 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 sprouting, it likely plays an important role, both temporally and spatially, in orchestrating postinjury events within the spinal cord. (C) 2000 Academic Press.