Intracerebral hematomas are commonly found in the gray matter or at boundaries between gray and white matter (Povlishock and Katz, 2005).
Disruption of the blood–brain barrier is a feature of TBI, including focal insults. Trauma produces physical damage to blood vessels, manifested in part by hemorrhage. Barrier disruption allows entry of toxic molecules while also providing an avenue for delivery of therapeutic agents into the damaged tissues (Saunders et al., 2008). It is the latter that has prompted investigators to define the window of barrier disruption better. There is evidence that the barrier to plasma-protein–size molecules is about 4 hours, whereas smaller molecules (smaller than 10 kDa) can access the brain for up to 4 days (Saunders et al., 2008). In the head-injured patient, disruption of the barrier is associated with life-threatening cerebral edema and is the basis of treatment with intravenous hyperosmolar solutions. However, the mechanism of action is not clearly understood, and there is no gold standard, on the basis of evidence from a clinical trial, of its effectiveness (Narayan et al., 2002).
Neuronal injury is also a feature of focal TBI. However, the patterns of neuronal injury are not necessarily restricted to contusional and pericontusional cortical sites (Raghupathi, 2004). Neuronal loss has been reported in more remote regions, including the hippocampus (Cortez et al., 1989; Kotapka et al., 1992; Lowenstein et al., 1992; Hicks et al., 1996), thalamus (Hicks et al., 1996; Sato et al., 2001), and the cerebellum (Sato et al., 2001; Park et al., 2006; Ai et al., 2007; Igarashi et al., 2007) in experimental models of TBI. Similar findings are seen in human TBI (Adams et al., 1985; Kotapka et al., 1992; Raghupathi, 2004).
At the contusional site, neuronal injury is apparent within hours after trauma. Neurons initially appear swollen and with time assume a shrunken phenotype bearing a pyknotic nucleus, swollen mitochondria, and vacuolated cytoplasm. The volume of the lesion expands coincidentally with a chronic pattern of neuronal degeneration (Colicos et al., 1996; Hicks et al., 1996; Bramlett et al., 1997; Conti et al., 1998; Raghupathi, 2004).
Four pathologic conditions have been attributed to diffuse TBI: traumatic axonal injury, hypoxic brain damage, brain swelling, and vascular injury (Morales et al., 2005; Povlishock and Katz, 2005). The disabling symptoms seen in TBI can arise from widespread traumatic axonal damage (Hurley et al., 2004; Morales et al., 2005) that is evident in postmortem brains after mild, moderate, or severe injury (Morales et al., 2005).