Caspase inhibition attenuates transection-induced oligodendrocyte apoptosis in the developing chick spinal cord.
A developmental model of spinal cord injury in the embryonic chick was specifically developed to characterize the involvement of caspases in injury-induced oligodendrocyte apoptosis remote from the lesion and the ability of caspase inhibitors to attenuate this process. Developmental apoptosis in the cervical spinal cord increased within the white matter between embryonic days 13 and 18, the period of myelination of this region. Spinal cord transection during this period induced a rapid increase in apoptotic cells in the ventral and lateral white matter over several millimeters caudal to the injury. Immunostaining identified large numbers of these cells as oligodendrocytes. Catalytic activity assays and immunostaining demonstrated caspase-3-like but not caspase-1-like activity to be involved in this apoptotic response. In vivo application of specific caspase inhibitors significantly attenuated transection-induced apoptosis. Thus, we describe a developmental period during which spinal oligodendrocytes exhibited a heightened, caspase-dependent sensitivity to transection-induced apoptosis that is attenuated by caspase inhibition.
McBride
Christopher B
CB
ICORD (International Collaboration On Repair Discoveries), University of British Columbia, Vancouver, British Columbia V6T 1Z4, Canada. mcbride@icord.org
McPhail
Lowell T
LT
Vanderluit
Jacqueline L
JL
Tetzlaff
Wolfram
W
Steeves
John D
JD
D000818:Animals; D017209:Apoptosis; D053148:Caspase 3; D061945:Caspase Inhibitors; D020169:Caspases / Q000378:metabolism; D002642:Chick Embryo; D002645:Chickens; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D004789:Enzyme Activation; D020287:In Situ Nick-End Labeling; D009413:Nerve Fibers, Myelinated / Q000473:pathology; D009836:Oligodendroglia / Q000201:enzymology / Q000473:pathology*; D009842:Oligopeptides / Q000494:pharmacology; D013116:Spinal Cord / Q000196:embryology* / Q000473:pathology*; D013119:Spinal Cord Injuries / Q000473:pathology*
D061945:Caspase Inhibitors; D015853:Cysteine Proteinase Inhibitors; D009842:Oligopeptides; C096429:L 709049; D053148:Caspase 3; D020169:Caspases