Reduction in CNS scar formation without concomitant increase in axon regeneration following treatment of adult rat brain with a combination of antibodies to TGFbeta1 and beta2.
In this study we investigated whether CNS axons regenerate following attenuation of scar formation using a combination of antibodies against two isoforms of transforming growth factor beta (TGFbeta). Anaesthetized adult rats were given unilateral mechanical lesions of the nigrostriatal tract. Implantation of transcranial cannulae allowed wounds to be treated with a combination of antibodies against TGFbeta1 and TGFbeta2 once daily for 10 days postaxotomy. Eleven days post-transection brains from animals under terminal anaesthesia were recovered for histological evaluation. Gliosis, inflammation and the response of dopaminergic nigral axons were assessed by immunolabelling. Treatment with antibodies against TGFbeta1 and TGFbeta2 attenuated (but did not abolish) the response of glial fibrillary acidic protein (GFAP)-immunoreactive astrocytes and of NG2-immunoreactive glia but did not attenuate the response of CR3-immunoreactive microglia and macrophages. However, this reduction in scar formation was not accompanied by growth of cut dopaminergic nigral axons. We conclude that treatment of injured adult rat brain with a combination of antibodies against TGFbeta1 and TGFbeta2 results in a reduction of scar formation but that this is not sufficient to enhance spontaneous long distance CNS axon regeneration.
Moon
L D
LD
Physiological Department, University of Cambridge, Downing Site, Cambridge, CB2 3EG, UK. lmoon@miamiproject.med.miami.edu
Fawcett
J W
JW
D000818:Animals; D000941:Antigens / Q000378:metabolism; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism; D001369:Axons / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D001930:Brain Injuries / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D002921:Cicatrix / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D005911:Gliosis / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D007150:Immunohistochemistry; D016177:Macrophage-1 Antigen / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D017628:Microglia / Q000187:drug effects / Q000378:metabolism; D017072:Neostriatum / Q000293:injuries / Q000473:pathology / Q000601:surgery; D009416:Nerve Regeneration / Q000187:drug effects* / Q000502:physiology; D009836:Oligodendroglia / Q000187:drug effects / Q000378:metabolism; D011509:Proteoglycans / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013234:Stem Cells / Q000187:drug effects / Q000378:metabolism; D013378:Substantia Nigra / Q000293:injuries / Q000473:pathology / Q000601:surgery; D016212:Transforming Growth Factor beta / Q000037:antagonists & inhibitors* / Q000378:metabolism; D053773:Transforming Growth Factor beta1; D053781:Transforming Growth Factor beta2; D000099216:Chondroitin Sulfate Proteoglycan 4
D000941:Antigens; D005904:Glial Fibrillary Acidic Protein; D016177:Macrophage-1 Antigen; D011509:Proteoglycans; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D053781:Transforming Growth Factor beta2; D000099216:Chondroitin Sulfate Proteoglycan 4; C508962:Tgfb1 protein, rat