A mapping study of caspase-3 activation following acute spinal cord contusion in rats.
Spinal cord injury (SCI) initiates a cascade of biochemical changes that results in necrotic and apoptotic cell death. There is evidence that caspase-3 activation and apoptotic cell death occur within hours after SCI. However, the time course and cellular localization of activated caspase-3 has not been examined. Such information is essential because caspase-3-independent apoptotic pathways do exist. In this experiment, we describe the distribution of and cell types containing activated caspase-3 at 4 hr, 1 day, 2 days, 4 days, and 8 days following SCI in rats. Numerous caspase-3-positive cells were observed at 4 hr and 1 day postinjury and colocalized most often with CC1, a marker for oligodendroglia. Both markers disappeared near the injury epicenter over the next several days. Activated caspase-3 was again present in the injured spinal cord on postoperative day 8, which coincided with a reemergence of CC1-positive cells. Many of these CC1-positive cells again colocalized activated caspase-3. NeuN-positive neurons of the dorsal horn were occasionally immunopositive for activated caspase-3 at early time points. OX42-positive microglia/macrophages rarely contained activated caspase-3. The results indicate a biphasic pattern of caspase-3 activation during the first 8 days postinjury, suggesting that at least two mechanisms activate caspase-3 following SCI. This time-course study provides a framework for investigating and understanding the different signaling events contributing to this biphasic pattern of caspase-3 activation.
Department of Physical Medicine and Rehabilitation, University of Kentucky Medical Center, Cardinal Hill Rehabilitation Hospital, 800 Rose St., MN 225, Lexington, KY 40536-0298, USA. mlmcew2@uky.edu
Melanie L
ML
McEwen
Joe E
JE
Springer
D000208:Acute Disease; D000818:Animals; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism*; D004789:Enzyme Activation; D005260:Female; D007150:Immunohistochemistry; D007796:Laminectomy; D008264:Macrophages / Q000201:enzymology / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009474:Neurons / Q000201:enzymology / Q000378:metabolism; D009836:Oligodendroglia / Q000201:enzymology / Q000378:metabolism; D051381:Rats; D020318:Rats, Long-Evans; D013116:Spinal Cord / Q000201:enzymology* / Q000378:metabolism; D013119:Spinal Cord Injuries / Q000201:enzymology* / Q000378:metabolism / Q000601:surgery
D009419:Nerve Tissue Proteins; C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases