Modeling Injury Severity

In contrast to the clinical situation, no commonly used scoring system for injury severity based on neurological examination has been adopted for the rodent. Therefore, the classification of mild, moderate, and severe experimental TBI continues to be based on measurements of the somewhat arbitrary mechanical injury parameters. Moreover, most injury devices are custom-made and show subtle differences. As a result, scoring systems based on mechanical parameters may be specific only for a particular laboratory. Additionally, different TBI impact sites produce a distinct pattern of injury-induced changes, making experimental findings from different centers difficult to compare at best. Besides these more technical difficulties, the whole heterogeneous spectrum of human TBI is broader than can possibly be modeled in the experimental setting, and both the posttraumatic sequelae after mild TBI without overt morphological damage and the severest cases of TBI with high mortality have not been comprehensively studied.

C. Survival Times and Outcome Measurements

The great majority of studies of experimental TBI have been conducted with short survival times in the range of hours or days. Although the results obtained in these studies may help us to gain insight into the acute posttraumatic sequelae, these histological or behavioral endpoints do not represent a valid assessment of long-term outcomes. Therefore, more studies evaluating injury response and behavioral deficits in the chronic phase (weeks or months after TBI) are warranted. Additionally, the limitations linked with neurobehavioral outcome measurements (high biological variability resulting in a high number of animals required, time- and cost-intensive) have restricted the number of studies evaluating behavioral outcomes after experimental TBI. Because the main effort in patient care is directed toward the attenuation of behavioral dysfunction and chronic disability, more research designed to evaluate neurobehavioral deficits and the therapeutic efficacy of new drugs to attenuate cognitive and neurologic motor functions after TBI is sorely needed.

Although robust impairments in neurologic motor function and cognition have been reported following TBI from moderate or severe magnitude, a great majority of patients suffer from mild clinical TBI. Although the majority of these mildly head-injured patients are not clinically observed or reported, a small percentage register complaints about postconcussive symptoms weeks and months after the traumatic insult. A thorough examination employing sensitive tests directed to detect impairments in higher cognitive or emotional function have indeed shown persistent deficits after mild clinical TBI. However, no such tests are available in the laboratory setting at present. Because the high incidence of mild TBI and the related long-term impairments warrant further investigation, more sensitive tests to elucidate the posttraumatic sequelae after experimental mild TBI must be developed.

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