Progressive damage after brain and spinal cord injury: pathomechanisms and treatment strategies

The pathophysiology of brain and spinal cord injury (SCI) is complex and involves multiple injury mechanisms that are spatially and temporally specific. It is now appreciated that many of these injury mechanisms remain active days to weeks after a primary insult. Long-term survival studies in clinically relevant experimental studies have documented the structural changes that continue at the level of the insult as well as in remote brain structures. After traumatic brain injury (TBI), progressive atrophy of both gray and white matter structures continues up to I year post-trauma. Progressive changes may therefore underlie some of the long-term functional deficits observed in this patient population. After SCI, similar features of progressive injury are observed including delayed cell death of neurons and oligodendrocytes, axonal demyelination of intact fiber tracts and retrograde tract degeneration. SCI also leads to supraspinal changes in cell survival and remote brain circuitry. The progressive changes in multiple structures after brain and SCI are important because of their potential consequences on chronic or developing neurological deficits associated with these insults. In addition, the better understanding of these injury cascades may one day allow new treatments to be developed that can inhibit these responses to injury and hopefully promote recovery. This chapter summarizes some of the recent data regarding progressive damage after CNS trauma and mechanisms underlying these changes.