Effects of transforming growth factor beta 1 on scar production in the injured central nervous system of the rat.
In the central nervous system (CNS), nerve regeneration after traumatic injury fails. The formation of a dense fibrous scar is thought to restrict in part the growth of axonal projections, providing one of the many reasons that complete lesions of neural pathways in the adult mammalian CNS are rarely followed by significant functional recovery. In order to determine which mechanisms mediate scar formation in the CNS and to investigate whether they can be modulated in vivo, we have attempted to define the potential role of trophic factors. Our previous studies have shown the focal elevation of transforming growth factor beta 1 (TGF beta 1) expression in lesioned CNS tissue. In the studies described here, we demonstrate that TGF beta 1 participates in the scarring response in the rat brain. First, the elevated protein levels of TGF beta 1 are localized to specific populations of injury-responsive cells in the traumatized CNS. Furthermore, the injection of TGF beta 1 into the brains of injured rats causes a dramatic increase in the scarring response. Conversely, when neutralizing TGF beta 1 antibodies are administered, the deposition of fibrous scar tissue and the formation of a limiting glial membrane that borders the lesion is significantly attenuated, thus establishing a role for the endogenous growth factor in regulation of the non-glial component of the scar. In implicating TGF beta 1 in the scarring response in the CNS, the potential use for TGF beta 1 antagonists as inhibitors of scar formation in the injured mammalian CNS is self-evident.
Department of Molecular and Cellular Growth Biology, Whittier Institute for Diabetes and Endocrinology, La Jolla, CA 92037.
A
A
Logan
M
M
Berry
A M
AM
Gonzalez
S A
SA
Frautschy
M B
MB
Sporn
A
A
Baird
D000818:Animals; D001930:Brain Injuries / Q000188:drug therapy* / Q000503:physiopathology; D002921:Cicatrix / Q000188:drug therapy* / Q000503:physiopathology; D005260:Female; D007150:Immunohistochemistry; D009416:Nerve Regeneration / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
D016212:Transforming Growth Factor beta