Calpain activity and expression increased in activated glial and inflammatory cells in penumbra of spinal cord injury lesion.
Following traumatic injury of the spinal cord, cells adjacent to the lesion are subject to ischemic cell death as a result of vascular disruption and secondary inflammatory responses. Proteases such as calcium-activated neutral proteinase (calpain) have been implicated in axon and myelin destruction following injury since they degrade structural proteins in the axon-myelin unit. To examine the role of calpain in cell death following spinal cord injury (SCI), calpain activity and translational expression were evaluated using Western blotting techniques. Calpain activity (as measured by specific substrate degradation) was significantly increased in and around the lesion site as early as 4 hr following injury with continued elevation at 48 hr compared to sham controls. Likewise, calpain expression was significantly increased in both the lesion site and penumbra at 4 and 48 hr after injury. Using double immunofluorescent labeling for calpain and cell-specific markers, this increase in calpain expression was found to be due in part to activated glial/inflammatory cells such as astrocytes, microglia, and infiltrating macrophages in these areas. Thus, since calpain degrades many myelin and axonal structural proteins, the increased activity and expression of this enzyme may be responsible for destruction of myelinated axons adjacent to the lesion site following SCI.
Shields
D C
DC
Department of Neurology, Medical University of South Carolina, 171 Ashley Avenue, Charleston, SC 29425, USA.
Schaecher
K E
KE
Hogan
E L
EL
Banik
N L
NL
D000818:Animals; D002154:Calpain / Q000276:immunology / Q000378:metabolism*; D016923:Cell Death / Q000502:physiology; D007249:Inflammation / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology*; D018836:Inflammation Mediators / Q000378:metabolism; D008264:Macrophages / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008297:Male; D017628:Microglia / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D009457:Neuroglia / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000276:immunology / Q000473:pathology / Q000503:physiopathology; D013119:Spinal Cord Injuries / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology*
D018836:Inflammation Mediators; D002154:Calpain