Temporal and spatial profiles of cell loss after spinal cord injury: Reduction by a metalloporphyrin

This study presents quantitative temporal and spatial profiles of neuronal loss and apoptosis following a contusion spinal cord injury (50 g . cm). The profiles were evaluated by counting the cresol violet-stained surviving cells and the total number of TUNEL-positive cells and of TUNEL-positive neurons in sections 0- 4 mm from the epicenter and 1, 6, 12, 24, 48, and 72 hr and 1 week postinjury. We demonstrated that neurons continue to disappear over 1 week postinjury and that neuronal loss shifts to areas longer distances from the epicenter over time. TUNEL-positive cells in both gray and white matter appeared after 6 hr, gradually increased to a peak level after 48 hr, and declined by 72 hr postinjury. TUNEL-positive neurons peaked earlier and were present for 1 week, although the total number of neurons was reduced significantly by the end of the week. The neuronal loss and apoptosis were partially prevented by a metalloporphyrin [Mn(III) tetrakis (4-benzoic acid) porphyrin (MnTBAP)]. We demonstrated that MnTBAP (10 and 50 mg/kg, given intraperitoneally) significantly reduced neuronal death in the sections 1-2.5 mm rostral and 1 mm caudal from the epicenter compared with that in the vehicle-treated group, suggesting MnTBAP is more effective in the sections rostral than in those caudal to the epicenter. MnTBAP (10 mg/kg) significantly reduced the number of TUNEL-positive neurons in the sections 1 mm caudal from the epicenter. Our profiles provide a database for pharmacological intervention, and our results on MnTBAP treatment support an important role for antioxidant therapy in spinal cord injury.