Tempol, a nitroxide antioxidant, improves locomotor and histological outcomes after spinal cord contusion in rats.
We have determined whether the nitroxide antioxidant, tempol, can oppose tissue loss and improve recovery of locomotor function following contusion injury of the spinal cord. Contusion injury was produced in rats at the level of T10 with a weight-drop device and locomotor recovery was determined with the 21-point Basso, Beattie and Bresnahan (BBB) scale. Locomotor function recovered progressively during the 6-week postinjury observation period and was significantly greater in tempol-treated (275 mg/kg i.p., 20 min postinjury) compared to vehicle-treated rats (final BBB scores: 9.1 versus 6.4). Similarly enhanced locomotor recovery was observed with doses of tempol in the range of 138-550, but not 69 mg/kg, and with injection at 48 h postinjury indicating a therapeutic time-window of at least several days. The extent of recovery correlated with measurements of sparing of spinal cord white matter in a region several millimeters in length extending rostrally from the contusion epicenter. In contrast, loss of gray matter was unaffected by tempol treatment. Since tempol acts by scavenging reactive oxygen species (ROS) such as superoxide and hydroxyl radicals, the improved locomotor recovery and spared spinal cord tissue following contusion injury provides evidence of a direct role of ROS-mediated neurodegeneration in spinal cord injury.
Hillard
Virany H
VH
Department of Neurosurgery, New York Medical College, Valhalla, New York 10595, USA.
Peng
Hong
H
Zhang
Yan
Y
Das
Kaushik
K
Murali
Raj
R
Etlinger
Joseph D
JD
Zeman
Richard J
RJ
D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use*; D003497:Cyclic N-Oxides / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D005260:Female; D009043:Motor Activity / Q000187:drug effects*; D009410:Nerve Degeneration / Q000188:drug therapy; D018696:Neuroprotective Agents / Q000627:therapeutic use; D051381:Rats; D020127:Recovery of Function / Q000187:drug effects*; D013113:Spin Labels; D013119:Spinal Cord Injuries / Q000188:drug therapy* / Q000473:pathology
D000975:Antioxidants; D003497:Cyclic N-Oxides; D018696:Neuroprotective Agents; D013113:Spin Labels; C001803:tempol