Temporal and spatial distribution of activated caspase-3 after subdural kainic acid infusions in rat spinal cord.
The molecular events initiating apoptosis following traumatic spinal cord injury (SCI) remain poorly understood. Soon after injury, the spinal cord is exposed to numerous secondary insults, including elevated levels of glutamate, that contribute to cell dysfunction and death. In the present study, we attempted to mimic the actions of glutamate by subdural infusion of the selective glutamate receptor agonist, kainic acid, into the uninjured rat spinal cord. Immunohistochemical colocalization studies revealed that activated caspase-3 was present in ventral horn motor neurons at 24 hours, but not 4 hours or 96 hours, following kainic acid treatment. However, at no time point examined was there evidence of significant neuronal loss. Kainic acid resulted in caspase-3 activation in several glial cell populations at all time points examined, with the most pronounced effect occurring at 24 hours following infusion. In particular, caspase-3 activation was observed in a significant number of oligodendroglia in the dorsal and ventral funiculi, and there was a pronounced loss of oligodendroglia at 96 hours following treatment. The results of these experiments indicate a role for glutamate as a mediator of oligodendroglial apoptosis in traumatic SCI. In addition, understanding the apoptotic signaling events activated by glutamate will be important for developing therapies targeting this cell death process.
Nottingham
Stephanie A
SA
Department of Anatomy and Neurobiology, Spinal Cord and Brain Injury Research Center, University of Kentucky Medical Center, Lexington, Kentucky 40536-0084, USA.
Springer
Joe E
JE
D000818:Animals; D000870:Anterior Horn Cells / Q000201:enzymology; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism*; D004789:Enzyme Activation; D018690:Excitatory Amino Acid Agonists / Q000008:administration & dosage*; D005260:Female; D007608:Kainic Acid / Q000008:administration & dosage*; D009046:Motor Neurons / Q000201:enzymology; D009457:Neuroglia / Q000201:enzymology; D009474:Neurons / Q000201:enzymology; D009836:Oligodendroglia / Q000201:enzymology; D051381:Rats; D020318:Rats, Long-Evans; D013116:Spinal Cord / Q000166:cytology / Q000201:enzymology*; D013355:Subdural Space; D013997:Time Factors; D014018:Tissue Distribution
D018690:Excitatory Amino Acid Agonists; C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases; D007608:Kainic Acid