ABSTRACT
The serious and long lasting impact of head injury has been recognized since the paleolithic era, but the potential for treatment of the injured brain has only manifested over the last 50 to 60 years as understanding of cell structure and function within the injured CNS has developed. This chapter reviews the development of ideas concerning the pathobiomechanical response(s) in axons of neurons following transient mechanical loading in central white matter of the CNS. Rather than axons being directly sheared at the time of an insult (primary axotomy), it is now recognized that a complex and incompletely understood series of cellular interactions occurs during hours and days following TBI that may lead to disconnection and disrupted function within and between neuronal networks or circuits, so termed secondary axotomy, following a single, rapid mechanical loading episode. This chapter reviews developments in the experimental literature concerning acute injury to the axolemma and the associated, uncontrolled influx of sodium and calcium ions, intra-axonal release of calcium from mitochondria and the axoplasmic reticulum, and the failure of axonal mitochondria leading to exacerbation of injury to cell membranes. The influx of free calcium into an injured axon mediates proteolysis of the subaxolemma and axonal cytoskeletons, axonal microtubules and neurofilaments. These are reviewed and the progression toward secondary axotomy
outlined. Terminal loss of the axonal cytoskeleton by granular degeneration during Wallerian degeneration is reviewed. The possible influences of axonal loss in the post-acute and chronic phases of TBI are reviewed.
