Treatment of spinal cord impact injury in the rat with transforming growth factor-β

Tyor, William R; Avgeropoulos, Nicholas; Ohlandt, George; Hogan, Edward L

« Previous Next »Journal of the Neurological Sciences
Volume 200, Issue 1 , Pages 33-41, 15 August 2002

Treatment of spinal cord impact injury in the rat with transforming growth factor-β

William R Tyor
- Corresponding author. Ralph H. Johnson VA Medical Center, 109 Bee Street, Charleston, SC 29401, USA. Tel.: +1-843-789-7428; fax: +1-843-937-6110
- Department of Neurology, Medical University of South Carolina, Charleston, SC, USA
- Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, SC, USA
Nicholas Avgeropoulos
- Department of Neurology, Medical University of South Carolina, Charleston, SC, USA
- Current address: Neurooncology Center,WDMCI at Florida Hospital, Suite 581, 2501 N. Orange Avenue, Orlando, FL 32804, USA.
George Ohlandt
- Department of Neurology, Medical University of South Carolina, Charleston, SC, USA
Edward L Hogan
- Department of Neurology, Medical University of South Carolina, Charleston, SC, USA

Received 8 February 2002; received in revised form 19 April 2002; accepted 22 April 2002.

Abstract

To investigate the contribution of cytokines, proinflammatory TNF-α and inhibitory TGF-β, to spinal cord injury (SCI) in a rat model, two studies were performed using adult Sprague–Dawley rats which were injured at T9/T10. In the first study, rats were sacrificed at 1, 6, 24, 96 and 168 h after SCI for immunocytochemistry of coronal sections for the presence of mononuclear phagocytes, astrocytes, TNF-α and TGF-β, among other markers. From intervening frozen sections, RNA was extracted for semiquantitative polymerase chain reaction (RT-PCR) analysis of TNF-α and TGF-β. In the second experiment, rats were treated with intravenous TGF-β 30 min after injury and sacrificed at 6 and 48 h after injury. Spinal cord sections were immunocytochemically stained and RNA extracted for semiquantitative PCR as mentioned above, as well as quantitation of lesion volume. There were increases in mononuclear phagocytes and astrocytes, as early as 1 h after SCI, with steady progression over 168 h after injury. TNF-α and TGF-β was produced locally by mononuclear phagocytes and astrocytes. There was an 18-h delay in peak mRNA production of TGF-β compared to TNF-α. The treatment of SCI rats with TGF-β reduced lesion volume by 50% at 48 h and this was associated with decreased accumulation of mononuclear phagocytes in and around the injury site. This reduction of mononuclear phagocyte numbers around the site of trauma would reduce their contribution to secondary injury.

Keywords: Spinal cord injury, Rats, Mononuclear phagocytes, Cytokines, Transforming growth factor-β