A head impact model of early axonal injury in the sheep.

Axonal injury (AI), one of the principal determinants of clinical outcome after head injury, may evolve over several hours after injury, raising the future possibility of therapeutic intervention during this period. A new head impact model of AI in sheep was developed to examine pathological and physiological changes in the brain resulting from a graded traumatic insult. In this preliminary study 10 anesthetized and ventilated Merino ewes were used. Head injury was produced by impact from a humane stunner to the temporal region of an unrestrained head. Eight sheep were studied for 1, 2, 4, or 6 h after impact. Two sham animals (no impact, 6 h survival) were also examined. Arterial blood pressure, intracranial pressure, and cerebral blood flow were monitored continuously. A physiological index of injury severity was calculated by weighting the percentage shift from preinjury values for each monitored parameter over the first hour after injury. Immunostaining with amyloid precursor protein (APP) was used as a marker of axonal damage and the distribution of APP positive axons was recorded according to a sector scoring method (APPS). Widespread AI was identified in 7 of the 8 impacted animals, around cerebral contusions and in hemispheric white matter, central gray matter, brain stem, and cerebellum, and was detected as early as 1 h after injury. The degree of axonal injury (APPS) correlated well with an index of physiological response to injury (r = 0.83, p = 0.005).