Neuroinflammation and the dynamic lesion in traumatic brain injury

Abstract

Until the latter half of the 20th century, moderate to severe traumatic brain injury (TBI) was rarely a survivable event (Masel and DeWitt, 2010). Fortunately, improvements in neuroimaging, and emergency medical and neurosurgical care have dramatically increased survival along with improved understanding and characterization of the acute effects of TBI. With improved survival, it was also assumed that understanding the acute effects of TBI would lead to strategies for better outcome, helpful in rehabilitation and more predictive of recovery or disability. During this era, standardizations emerged to categorize acute TBI by severity, most commonly based on the Glasgow Coma Scale, whether loss of consciousness occurred, duration of post-traumatic amnesia, presence/absence of skull fracture and neuroimaging findings. Because TBI has an obvious aetiology and onset, classic and well-defined neuropathologies from initial injury through chronic phases have been well characterized, including the macroscopic pathologies identified using neuroimaging. In fact, considerable optimism emerged that, as neuroimaging methods improved, detection of TBI-related pathologies such as cerebral oedema, contusions, intraparenchymal haemorrhages, epidural and subdural haematomas, that better predicted long-term outcome would occur. However, modelling long-term TBI outcome, in particular cognitive outcome, has proved elusive, even taking into account all of the acute TBI variables. Understanding outcome amounts to more than the severity of injury or even the size, type and location of traumatic lesions. What may be missing in TBI outcome models reveals an incomplete understanding of how these lesions influence neural networks of the functioning brain (Caeyenberghs et al., 2012). In other words, how well a patient with TBI returns to pre-injury level of function may depend most on how well functional neural networks survive and/or adapt to the injury. Networks depend on white matter integrity and therefore understanding white matter pathology is crucial in understanding TBI outcome. As elegantly described many years ago, white …