Enhanced expression of transforming growth factor beta 1 in the rat brain after a localized cerebral injury.
It is becoming clear that transforming growth factor beta (TGF beta) may be a key factor regulating inflammatory and tissue specific wound responses. Because the formation of a glial-collagen scar at CNS lesion sites is thought to contribute to the pathology associated with penetrating CNS injuries, and because in the periphery TGF beta 1 stimulates fibroblast deposition of scar tissue, we used in situ hybridization and immunohistochemistry to investigate the effect of a defined cerebral lesion on the local expression of TGF beta 1. Induction of TGF beta 1 mRNA and protein is relatively diffuse in the neuropile around the margins of the lesion at 1, 2 and 3 days, but becomes localized to the region of the glial scar at 7 and 14 days. The signal intensity for TGF beta 1 mRNA and protein is maximal between 2 and 3 days and decreases between 7 and 14 days after lesion. The predominant cell types in the neuropile localizing TGF beta 1 mRNA and protein have the morphological characteristics of astrocytes, although macrophages are also detected. An induction of TGF beta 1 mRNA was also observed in endothelial cells of the meninges, hippocampal fissure and choroid plexus, at 2 and 3 days. However, this is dramatically reduced by 7 days and has disappeared by 14 days. These results suggest a role for TGF beta 1, not only in inflammation, but also in the tissue-specific glial scar formation that occurs in the CNS. Furthermore, they suggest a potential therapeutic use of TGF beta 1 antagonists in the CNS to help limit the pathogenesis associated with matrix deposition in the wound.
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Department of Molecular and Cellular Growth Biology, Whittier Institute for Diabetes and Endocrinology, La Jolla, CA 92037.
Frautschy
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SA
Gonzalez
A M
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Sporn
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Baird
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D000818:Animals; D001921:Brain / Q000378:metabolism*; D001930:Brain Injuries / Q000378:metabolism* / Q000473:pathology; D002196:Capillaries / Q000378:metabolism; D003337:Corpus Callosum / Q000378:metabolism; D007124:Immunoenzyme Techniques; D007150:Immunohistochemistry; D008297:Male; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D011919:Rats, Inbred Strains; D016212:Transforming Growth Factor beta / Q000096:biosynthesis*
D012333:RNA, Messenger; D016212:Transforming Growth Factor beta