BIOMECHANICS OF A SHEEP MODEL OF AXONAL INJURY

The aim of this project was to investigate the feasibility of using an animal model of axonal injury to study the biomechanics of the injury. The model utilises anaesthetised sheep that are mechanically ventilated and stabilised before being subjected to a single lateral impact from a captive bolt gun. The impact force was measured using a load cell mounted in the striker, and the resulting head acceleration was measured by means of a 9accelerometer array which was rigidly mounted to the head of the sheep. Head kinematics were transformed to anatomical co-ordinates using stereo-radiography. High speed cine film (1000 fps) was used for the visualisation of gross head motion. After impact, each animal was allowed to survive for a predetermined period during which anaesthesia was maintained. A complement of physiological monitors was used to measure the physiological state of the animal at all times during the experiment. In one experiment, hypoxia was induced after the physical insult. After the survival period, the animal was sacrificed and the brain removed for histological processing. The brain was sectioned, processed and examined for axonal injury using the presence of amyloid precursor protein (APP) as an indicator of injury. The distribution of axonal injury in serial sections of the brain was mapped and quantified. Five experiments, displaying a range of injury responses, are reported on in this paper. In the future, the model will be used to study the biomechanics of axonal injury. All experiments conform to the Australian Code of Practice for the Care and Use of Animals for Scientific Purposes. AMONG PERSONS SUSTAINING A HEAD INJURY, axonal injury is a major cause of mortality and morbidity (Gennarelli, 1984) . There is evidence that it occurs across the spectrum of head injury severity (Blumbergs et al., 1994) . Yet it remains unclear to what extent different mechanical parameters contribute to the incidence of axonal injury, and how post impact physiological changes relate to the eventual severity of axonal injury. There have been many biological studies which have correlated the incidence of ‘diffuse type’ brain injuries (which includes axonal injury) with loading parameters. These types of studies have included isolated tissue studies, studies of single tracts of axons, direct percussion of the brains of small animals, and inertial loading of the head of larger animals. Animal models have the advantage that they are more likely to be better physiological representations of the human brain that isolated axon preparations. Isolated tissue studies are usually more simple to model biomechanically, however. Several investigators have used utilised single axons or single bundles of axons to study the response of the axon to loading. These studies have shown that direct mechanical loading of axons can lead to physiological changes in the cell such as rises in intracellular calcium (Saatman and Thibault, 1991) and increased rate of glucose metabolism (Gennarelli et al., 1989). Such models have also produced clear evidence that applied loads that are less than that required to cause primary axotomy may result in marked histological changes (Gennarelli et al., 1989). If brain tissue deformation can produce