The effects of treatment with antibodies to transforming growth factor beta1 and beta2 following spinal cord damage in the adult rat.
We recently showed axonal ingrowth into fibronectin (FN) mats implanted into the spinal cord. However, little axonal growth was found from FN mats into intact spinal cord. Previous research has shown that this is due in part to astrocytosis around an area of CNS damage. Antibodies to transforming growth factor beta (TGFbeta) can diminish this astrocytosis. TGFbeta also has effects on macrophages and Schwann cells, both of which infiltrate the spinal cord following damage. We examined the axonal, Schwann cell, and macrophage infiltration into FN mats as well as the level of astrocytosis and chondroitin sulfate proteoglycan NG2 around FN implants incubated in TGFbeta antibodies and implanted into a lesion cavity in the spinal cord. We also examined the effects of applying TGFbeta antibodies to a spinal cord hemisection site. Anti-TGFbeta1 within FN mats resulted in extensive cavitation, with the area of damage being larger than the original lesion. Cavitation was also seen following application of anti-TGFbeta1 to a spinal cord hemisection site. No cavitation was seen following saline, non-immune IgG or anti-TGFbeta2 treatment. However, anti-TGFbeta2 treatment did result in diminished axonal growth and Schwann cell and macrophage infiltration. Around the implant site, anti-TGFbeta2 treatment resulted in a reduction in the level of astrocytosis but had not effect on levels of NG2. Similar effects were seen following anti-TGFbeta2 application to spinal cord hemisection sites. The results suggest that anti-TGFbeta1 exacerbates secondary damage by preventing the anti-inflammatory effect of endogenous TGFbeta1. Anti-TGFbeta2 did not enhance axonal regeneration in this model but did slightly reduce astrocytosis.
King
V R
VR
Department of Neuroscience, St. Bartholomew's and the Royal London School of Medicine and Dentistry, Queen Mary College, University of London, Mile End Road, London E1 4NS, UK. vonrking@yahoo.co.uk
Phillips
J B
JB
Brown
R A
RA
Priestley
J V
JV
D000818:Animals; D000906:Antibodies / Q000494:pharmacology*; D001253:Astrocytes / Q000473:pathology; D008264:Macrophages / Q000473:pathology; D008297:Male; D009416:Nerve Regeneration / Q000276:immunology; D051381:Rats; D017208:Rats, Wistar; D012583:Schwann Cells / Q000473:pathology; D013119:Spinal Cord Injuries / Q000473:pathology* / Q000628:therapy*; D016212:Transforming Growth Factor beta / Q000276:immunology*; D053773:Transforming Growth Factor beta1; D053781:Transforming Growth Factor beta2; D017211:Treatment Failure
D000906:Antibodies; C508962:Tgfb1 protein, rat; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D053781:Transforming Growth Factor beta2