Diffuse axonal injury induced by simultaneous moderate linear and angular head accelerations in rats

Abstract

Diffuse axonal injury (DAI) is one of the most common and important pathologic features of human traumatic brain injury (TBI), accounting for high mortality and development of persistent post-traumatic neurologic sequelae. Although a relatively high number of therapies have been shown to be effective in experimental models, there are currently few treatments that are effective for improving the prognosis of clinical DAI. A major reason is the failure of current models to validly reproduce the pathophysiological characteristics observed after clinical DAI. In the present study, we employed a specially designed, highly controllable model to induce a sudden rotation in the coronal plane (75 degrees rotation at 1.6×10 4 degrees/s) combined with lateral translation (1.57 cm displacement at 3.4×10 2 cm/s) to the rat's head. We were interested in discovering whether the combined accelerations could reproduce the pathophysiological changes analogous to those seen in human DAI. The axonal injury as assessed with amyloid protein precursor (APP) as a marker was consistently present in all injured rats. The commonly injured brain regions included the subcortical regions, deep white matter, corpus callosum and brain stem. The evolution of APP accumulations in brain sections depicted the detailed progression of axonal pathology. Ultrastructural studies gave further insights into the presence and progression of axonal injury. All injured rats exhibited transient physiological dysfunction, as well as immediate and dramatic neurological impairment that still persisted at 14 days after injury. These results suggest that this model reproduced the major pathophysiological changes analogous to those observed after severe clinical TBI and provides an attractive vehicle for experimental brain injury research.