Proteolysis of Submembrane Cytoskeletal Proteins Ankyrin-G and αII-Spectrin Following Diffuse Brain Injury: A Role in White Matter Vulnerability at Nodes of Ranvier

A high membrane-to-cytoplasm ratio makes axons particularly vulnerable to traumatic injury. Posttraumatic shifts in ionic homeostasis promote spectrin cleavage, disrupt ankyrin linkages and destabilize axolemmal proteins. This study contrasted ankyrin-G and alpha II-spectrin degradation in cortex and corpus callosum following diffuse axonal injury produced by fluid percussion insult. Ankyrin-G lysis occurred preferentially in white matter, with acute elevation of all fragments and long-term reduction of a low kD form. Calpain-generated alpha II-spectrin fragments increased in both regions. Caspase-3 lysis of alpha II-spectrin showed a small, acute rise in cortex but was absent in callosum. White matter displayed nodal damage, with horseradish peroxidase permeability into the submyelin space. Ankyrin-G-binding protein neurofascin and spectrin-binding protein ankyrin-B showed acute alterations in expression. These results support ankyrin-G vulnerability in white matter following trauma and suggest that ankyrin-G and alpha II-spectrin proteolysis disrupts Node of Ranvier integrity. The time course of such changes were comparable to previously observed functional deficits in callosal fibers.