Inhibition of TGF-beta1 promotes functional recovery after spinal cord injury.
Trauma to the spinal cord initiates a series of cellular and biochemical processes that damage both neurons and glia. TGF-beta and its receptors are expressed around the injury site following a spinal cord injury. Here, we report that the intrathecal administration of a neutralizing antibody to TGF-beta1 in rats with thoracic spinal cord contusion results in a significant enhancement of the locomotor recovery. The inhibition of TGF-beta1 suppresses glial scar formation and upregulates microglia/macrophage activation after the injury, presumably providing a favorable environment for restoration of the neural network. Rats treated with the anti-TGF-beta1 antibody exhibited a mild enhancement of growth and/or preservation of axons in the injured spinal cord caudal to the site of contusion. These results support the possibility of using TGF-beta1 inhibitors in the treatment of human spinal cord injuries.
Kohta
Masaaki
M
Department of Molecular Neuroscience, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan.
Kohmura
Eiji
E
Yamashita
Toshihide
T
D000818:Animals; D057134:Antibodies, Neutralizing / Q000627:therapeutic use*; D005260:Female; D007150:Immunohistochemistry; D008262:Macrophage Activation / Q000187:drug effects; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D017628:Microglia / Q000276:immunology / Q000378:metabolism; D009416:Nerve Regeneration / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function; D013119:Spinal Cord Injuries / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism*; D053773:Transforming Growth Factor beta1 / Q000037:antagonists & inhibitors*
D057134:Antibodies, Neutralizing; C508962:Tgfb1 protein, rat; D053773:Transforming Growth Factor beta1