A Mapping Study of Caspase-3 Activation Following Acute Spinal Cord Contusion in Rats

• Published in: The journal of histochemistry and cytochemistry 2005-07, Vol.53 (7), p.809-819
• Main Authors: McEwen, Melanie L, Springer, Joe E
• Format: Article
• Language: English
• Subjects: Acute Disease; Animals; Caspase 3; Caspases - metabolism; Enzyme Activation; Female; Immunohistochemistry; Laminectomy; Macrophages - enzymology; Macrophages - metabolism; Nerve Tissue Proteins - metabolism; Neurons - enzymology; Neurons - metabolism; Oligodendroglia - enzymology; Oligodendroglia - metabolism; Rats; Rats, Long-Evans; Spinal Cord - enzymology; Spinal Cord - metabolism; Spinal Cord Injuries - enzymology; Spinal Cord Injuries - metabolism; Spinal Cord Injuries - surgery
• ISSN: 0022-1554; 1551-5044
• DOI: 10.1369/jhc.4A6467.2005

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.