TRAUMATIC BRAIN INJURY

The GCS assesses motor, verbal and eye responses; while there is some variability in the categories, a GCS  from 13 to 15 is often designated as mild TBI, 8 or below is considered severe, and 9 to 12 is considered a moderate TBI (Jennett, 1998; Parikh et al., 2007).

There are two common conjec- tures regarding the etiology of mTBI. The first is that the frontal and an- terior cortices are vulnerable to neural contusion (Adams et al., 1980; Beaumont and Gennarelli, 2006; Brandstack et al., 2006; Levin et al., 1992). The second is that linear and rotational forces act on axon bun- dles, leading to axonal injury (Buki and Povlishock, 2006; Gennarelli et al., 1982; Meythaler et al., 2001; Povlishock et al., 1992). After initial injury, secondary mechanisms elicit biochemical, metabolic, and cellu- lar changes in the time frame of minutes, days and months (Giza and Hovda, 2001; Loane and Faden, 2010; Xiong et al., 1997).  

Although mTBI has long been considered a noncritical injury, serious short and long term effects have been documented.  

Traumatic brain injury (TBI) occurs when a traumatic event causes the brain to move rapidly within the skull, leading to damage. As illustrated in the poster (panel A), the event can be classified as either impact or non-impact, depending on whether the head makes direct contact with an object (impact) or encounters a non- impact force such as blast waves or rapid acceleration and deceleration (non-impact).

Currently, the severity of TBI is categorized based on the Glasgow Coma Scale (GCS), in which patients are scored on the basis of clinical symptoms, and the resulting overall score classifies their injury as mild (score: 13-15), moderate (score: 9-12) or severe (score: <9). 

Symptoms of mild to moderate TBI can include headaches, dizziness, nausea and amnesia; these injuries usually resolve within days to weeks of the insult. 

However, occasionally these injuries can result in long-term cognitive and behavioral deficits. Furthermore, there is evidence to suggest that moderate to severe TBI, and even repeat mild TBI, might be associated with increased risk of neurodegenerative diseases such as Alzheimer’s disease (Lye and Shores, 2000), chronic traumatic encephalopathy (McKee et al., 2009) and Parkinson’s disease (Hutson et al., 2011). 

Primary injury refers to the initial impact that causes the brain to be displaced within the skull. Secondary injuries gradually occur as a consequence of ongoing cellular events that cause further damage. Fluid percussion (FP), controlled cortical impact (CCI) and weight-drop injury are the most commonly used TBI models that can be modulated to generate injuries with characteristics of mild or severe TBI 

During the acute phase (≤1 hour) after TBI, there is a massive release of glutamate from presynaptic terminals, which disrupts ionic equilibrium on postsynaptic membranes. The amount of potassium (K+) released increases with injury severity, as measured by microdialysis (Katayama et al., 1990; Kawamata et al., 1992). 

In addition to rising [K+], calcium (Ca2+) accumulation is also commonly observed after TBI (Osteen et al., 2001). Accumulation of intracellular Ca2+ activates mitochondrial Ca2+ uptake. Ca2+ overloading of the mitochondria has been shown to induce oxidative stress and to impair mitochondrial function (Xiong et al., 1997; Peng and Jou, 2010).  

Increases in 45Ca2+ were seen as early as 6 hours after the initial injury, and a return to control levels has been observed between 4 days (Fineman et al., 1993) and 7 days (Deshpande et al., 2008) post-injury. Ca2+ accumulation corresponded with the presence of cognitive deficits, which were detected using the spatial memory task, the Morris water maze.