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

• Published in: Journal of the neurological sciences Vol. 200; no. 1; pp. 33 - 41
• Main Authors: Tyor, William R, Avgeropoulos, Nicholas, Ohlandt, George, Hogan, Edward L
• Format: Journal Article
• Language: English
• Published: Shannon Elsevier B.V 15.08.2002; Elsevier Science
• Subjects: Animals; Biological and medical sciences; Cytokines; Cytokines - analysis; Female; Immunohistochemistry; Injuries of the nervous system and the skull. Diseases due to physical agents; Macrophages - metabolism; Medical sciences; Mononuclear phagocytes; Neuropharmacology; Neuroprotective agent; Pharmacology. Drug treatments; Rats; Rats, Sprague-Dawley; Spinal Cord Injuries - drug therapy; Spinal Cord Injuries - metabolism; Spinal cord injury; Stereotaxic Techniques; Time Factors; Transforming Growth Factor beta - biosynthesis; Transforming Growth Factor beta - therapeutic use; Transforming growth factor-β; Traumas. Diseases due to physical agents; Tumor Necrosis Factor-alpha - biosynthesis; Rats; Mononuclear phagocytes; Cytokines; Spinal cord injury; Transforming growth factor-β; Immunohistochemistry; Volumetric analysis; Spinal cord; Rat; Transforming growth factor β; Mononuclear cell; Evolution; Tumor necrosis factor α; Nervous system diseases; Pathophysiology; Cytokine; Rodentia; Neuroprotective agent; Astrocyte; Trauma; Pathology; Vertebrata; Chemotherapy; Mammalia; Treatment; Animal; Central nervous system disease; Morphometry; Spinal cord disease; Phagocyte
• ISSN: 0022-510X; 1878-5883
• DOI: 10.1016/S0022-510X(02)00113-2

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.