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

Abstract

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 αII‐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 αII‐spectrin fragments increased in both regions. Caspase‐3 lysis of αII‐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 αII‐spectrin proteolysis disrupts Node of Ranvier integrity. The time course of such changes were comparable to previously observed functional deficits in callosal fibers.