The serious and long lasting impact of @entity542 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 @entity131 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 @entity130 and the associated, uncontrolled influx of @entity1372 and @entity460 ions, intra-axonal release of @entity460 from mitochondria and the axoplasmic reticulum, and the failure of axonal mitochondria leading to exacerbation of injury to cell membranes. The influx of free @entity460 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 @entity528 during @entity6441 is reviewed. The possible influences of axonal loss in the post-acute and chronic phases of @entity131 are reviewed. Injury to the head and brain has been recognized as a serious clinical scenario since the Paleolithic era (Gross, 2003), and treatment by trepanation of part of the skull was an established and widely practiced therapeutic intervention in Greek and Roman civilizations (Missios, 2007). Hippocrates (460   377 BCE), conventionally described as being the father of medicine, provided a major contribution toward the development of neurosurgery in the classical era by publication of    On @entity542    written around 400 BCE (Missios, 2007). Hippocrates and his students developed a ranking of five subtypes of injury to the head: (1) a @entity79 with a fissured @entity174 ; (2) a simple @entity79 without @entity174 ; (3) @entity13668 ; (4) dinted @entity174 induced by a blow to the head by a weapon leaving an indentation or    hedra    (         a   ); and (5) most pertinent to this review,    injuries at distant sites.    Importantly, Hippocrates recognized that @entity1545 may occur in a different part of the brain from a primary wound to the surface of the head. Furthermore, it was widely recognized that wounds to the head were especially dangerous and that @entity204 was a high-risk sequel of severe @entity542 . This chapter will review changes in thinking about the mechanisms and/or causes of @entity1545 developed through the use of experimental models of @entity131 ( @entity131 ) and the appreciation at a clinical scenario of an increased understanding of @entity131 , the ability to monitor and assess progression of pathology within the injured brain, and the outcomes that a @entity1 and their family may anticipate during posttraumatic survival.

Development of Concepts in the Pathology of Traumatic Axonal and Traumatic XXXX

@entity1545 :: ('MESH:D020214', 'Disease') :: ['injury to the brain'] @entity1 :: ('9606', 'Species') :: ['patient'] @entity131 :: ('MESH:D001930', 'Disease') :: ['TBI', 'traumatic brain injury'] @entity13668 :: ('MESH:D020204', 'Disease') :: ['depressed skull fractures'] @entity174 :: ('MESH:D050723', 'Disease') :: ['fractures', 'fracture'] @entity542 :: ('MESH:D006259', 'Disease') :: ['Injuries to the Head', 'head injury'] @entity1372 :: ('MESH:D012964', 'Chemical') :: ['sodium'] @entity79 :: ('MESH:D001847', 'Disease') :: ['bone contusion'] @entity460 :: ('MESH:D002118', 'Chemical') :: ['calcium'] @entity6441 :: ('MESH:D014855', 'Disease') :: ['Wallerian degeneration'] @entity204 :: ('MESH:D003643', 'Disease') :: ['death'] @entity528 :: ('MESH:D009410', 'Disease') :: ['granular degeneration'] @entity130 :: ('MESH:D014947', 'Disease') :: ['injury to the axolemma']
@entity1545 :: (MESH:D020214,Disease) :: ['Brain Injury']
