(Wieloch and Nikolich, 2006). Efforts have been made to reverse secondary pathogenesis with an emphasis on extending treatment beyond the acute injury into this recovery phase (Kokiko and Hamm, 2007). One result is the concept that enhancing neuronal activity may facilitate cognitive recovery (Kokiko and Hamm, 2007). Strategies to support recovery also include early activation of noradrenergic, dopaminergic, and cholinergic pathways to promote functional plasticity and growth factors to support plasticity; cortical stimulation and physical therapy can enhance recovery during the chronic phase (Wieloch and Nikolich, 2006).
On the basis of the complex pathophysiology of TBI, there has been a concerted effort to develop biomarkers of injury that would serve as both diagnostic and prognostic measures of injury or recovery (Kochanek et al., 2008). The availability of cerebrospinal fluid, brain tissue, and interstitial fluid from both experimental models of TBI and brain-injured patients has made it possible to identify candidate biomarkers. Putative serum biomarkers of interest have included cyclic adenosine monophosphate, thought to be an indicator of depth of coma, and neuron-specific enolase, myelin basic protein, and S100B, markers of structural damage. In more recent years, proteomics and multibead technology, based on multiple enzyme immunosorbent assays, have been developed to assay multiple proteins from a relatively small sample. Those advanced technologies offer the opportunity to track the complex injury cascade that accompanies TBI and ultimately to generate a panel of biomarkers that can be applied to the brain-injured patient.
TBI may be classified according to the extent of the pathology of the injury or according to the biomechanics of the injury. Both these classifications are discussed below.
TBI has been described pathologically as focal and/or diffuse (Smith et al., 2003; Werner and Engelhard, 2007) (Figure 2.1). Focal damage is characterized by cerebral contusions resulting from forces related to impact (Povlishock and Katz, 2005). Contrecoup contusion may be apparent but is thought to be a consequence of acceleration and deceleration rather than impact (Graham et al., 2002). Diffuse injuries arise from rapid rotations of the head that result in tissue distortion or shear and typically occur in motor-vehicle collisions and less often in falls and assaults (Smith et al., 2003; Morales et al., 2005).
It is important to emphasize that focal and diffuse injuries overlap (Povlishock and Katz, 2005). Human TBI, particularly severe TBI, is heterogeneous (Graham et al., 2000; Faden, 2002). It is unusual to find a single lesion and more common to find both focal and diffuse patterns of damage. Moreover, the number of lesions increases in proportion to the severity of the injury and correlates with morbidity (Graham et al., 2000).
Focal injuries are evidenced by lacerations, contusions, and hematomas resulting from overt vascular damage (Morales et al., 2005). Localization of a hematoma depends in part on which elements of the vascular tree are injured. Rupture of meningeal vessels, bridging veins, and intrinsic vasculature leads to extradural, subdural, and intracerebral hematomas, respectively.