Injury Severity

The most commonly used clinical classification for human head injury is based on the Glasgow Coma Scale, which allows clinicians to divide admitted patients into three major categories of mild (score higher than 13), moderate (score between 9 and 12), and severe TBI (score below 9). Studies conducted to define and characterize outcomes in each of these three categories that can be used to predict spontaneous outcome and response to therapeutic intervention have proven its reliability and usefulness. To closely mimic the range of TBI severity in the clinical situation, experimental studies have modified the existing injury models to be capable of producing brain trauma over a spectrum of severity. This goal is accomplished by adjusting the main mechanical parameters of the injury device (e.g., height or mass of the free-falling weight, depth of the traumatic impact or impact velocity, height of the pressure impulse by adjusting the pendulum of the fluid-percussion device, or changes in the plane or velocity of the rotational forces). Although a scoring method for injury severity comparable to the Glasgow Coma Scale has been developed for the cat, it has yet to be defined for the rodent. However, a number of experimental studies performed have exposed a close relationship between injury severity and the animals' posttraumatic responses and rates of recovery. As a result, a classification for the severity of experimental TBI has been developed and established that is similar to the clinical categories of mild, moderate, and severe.

B. Types of Injury

Human head injury is not a single pathophysiological entity, and the majority of patients suffering from TBI display more than one lesion upon careful diagnostic evaluation. Because the clinical situation is seldom as controlled as the experimental setting, different injury models are employed to elucidate the main characteristics of TBI, which include focal and diffuse damage. Focal abnormalities involve contusions and lacerations not always accompanied by skull fracture or hematoma formation. This type of damage occurs in the direct vicinity of the site of mechanical impact to the head and typically involves the underlying cortical and, in the case of injuries of higher severity, subcortical structures. Several experimental models have been established that mimic these aspects of focal TBI over a wide range of injury severity (weight-drop closed head injury, fluid-percussion brain injury, and rigid indentation injury). However, all models are associated with concussive events, and, if the injury severity exceeds a certain threshold, substantial displacement of the brain occurs, which adds a new, more remote component of axonal injury to the predominantly focal damage (Fig. 1). Diffuse injuries may include concussions and diffuse axonal pathology. This type of injury is sometimes more difficult to detect in the clinical setting but appears to occur more commonly than previously believed and is presumably present in the whole range from mild to severe head injury. Diffuse brain injuries are thought to occur primarily from the tissue distortion, or shear, caused by inertial forces that are present at the moment of injury. Experimental models that predominantly mimic this type of damage (e.g., models of inertial acceleration and, to a lesser extent, impact acceleration) lead to substantial diffuse injury in the absence of profound focal damage. These changes are usually observed peripheral to the vicinity of the impact and also remote to the injury site (Fig. 1).

C. Determining Injury-Induced Changes and Outcome

A number of scales have been created to evaluate spontaneous and therapeutically modified

Figure 1 Injury characteristics of different experimental models to produce TBI. Each model produces a distinct pattern of focal and/or diffuse brain injury.

posttraumatic recovery, characterize permanent deficits, or estimate life quality in the chronic phase after clinical TBI. Although a satisfactory system to determine outcome of head-injured patients has yet to be described, the Glasgow Outcome Scale, which divides patients into five subgroups according to their level of recovery or persisting impairment, seems to be the most popular and widely accepted scoring method at present. Thorough evaluation of patients has made it unequivocally clear that behavioral impairments, particularly with respect to neurologic motor function and cognitive deficits, comprise the most persistent deficits after TBI, lasting for months and even years. Additionally, a number of radiological and histologi-cal studies have revealed that morphological damage to the brain tissue represents another very consistent feature of human TBI that remains unresolved and persists over time. In contrast, a broad variety of different posttraumatic events occur in the immediate and acute phase after TBI (e.g., changes in electro-physiology, blood-brain barrier dysfunction, edema formation, changes in cerebral perfusion and intracra-nial pressure, activation of ion channels and ion shift, genomic changes, production of free radicals, inflammation, etc.). Some of these changes are transient, but the duration of others has yet to be determined. To follow and describe injury-induced changes in the experimental setting, research tools have been developed to determine both the reversible and the persistent posttraumatic sequelae after experimental TBI in the laboratory (Table I). Although the great majority of experimental studies have been conducted with posttraumatic survival times of hours or days, a smaller number of studies have successfully identified persistent neurobehavioral impairments and histolo-gical changes in the chronic phase after experimental TBI up to 1 year postinjury. Because these persisting alterations (morphologic and behavioral changes)

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