Balentine J D
Department of Pathology and Laboratory Medicine, Medical University of South Carolina, Charleston 29425.
J Neuropathol Exp Neurol. 1988 Mar;47(2):77-92. doi: 10.1097/00005072-198803000-00001.
The rapid appearance of selective axonal calcification following experimentally induced spinal cord impact injury has suggested that there is a sudden influx of intracellular calcium which mediates many of the pathological changes subsequent to the trauma. Granular dissolution of axoplasm and vesicular disruption of myelin are the most characteristic alterations in the affected white matter. These changes, which appear early and progress, are identical to those that can be induced by exposing myelinated axons to increased extracellular calcium or to calcium ionophores. These observations have led us to develop the hypothesis that calcium mediates the destruction of traumatized axons in the spinal cord by stimulating calcium-activated neutral proteinases (CANP), which in turn degrade axonal and myelin proteins. A rapid increase in CANP activity has been demonstrated in our experimental rat trauma model and a CANP has been isolated from rat spinal cord myelin which degrades both neurofilament and myelin proteins. However, the interpretation of the role of calcium has been complicated by the fact that granular axoplasm and vesicular myelin can be induced under conditions other than those favorable for CANP enhancement. The ultimate proof of the calcium hypothesis will depend on analyzing early intracellular ionic fluxes and correlating these with the localization of calcium-mediated enzymes and the evolution of pathological events.
