Concussion in professional football: morphology of brain injuries in the NFL concussion model--part 16.

OBJECTIVE: An animal model of concussions in National Football League players has been described in a previous study. It involves a freely moving 300-g Wistar rat impacted on the side of the head at velocities of 7.4 to 11.2 m/s with a 50-g impactor. The impact causes a 6% to 28% incidence of meningeal hemorrhages and 0.1- to 0.3-mm focal petechiae depending on the impact velocity. This study addresses the immunohistochemical responses of the brain. METHODS: Twenty-seven tests were conducted with a 50-g impactor and velocities of 7.4, 9.3, or 11.2 m/s. The left temporal region of the helmet-protected head was hit I or 3 times. Thirty-one additional tests were conducted with a 100-g impactor. Diffuse axonal injury in distant regions of the brain was assessed with immunohistochemistry for NF-200, the heaviest neurofilament subunit, and glial fibrillary acidic protein, an intermediate filament protein in astrocytes. Hemorrhages were analyzed by unspecific peroxidase. There were 10 controls. RESULTS: A single impact at 7.4 and 9.3 m/s velocity with the 50-g impactor causes minimal neuronal injury and astrocytosis. Repeat impacts with 11.2 m/s velocity and more than 9.3-m/s impacts with 100 g cause diffuse axonal injury and distant injury bilaterally in the cerebral cortex, the subcortical, the white matter, the hippocampus CA1, the corpus callosum, and the striatum, as indicated by NF-200 accumulation in neuronal perikarya 10 days after impact. It also causes reactive astrocytosis in the midline regions of the cerebral cortex and periventricularly. Regions with erythrocyte-loaded blood capillaries indicated brain edema in regions of the cerebral cortex, the brainstem, and the cerebellum. CONCLUSION: When the immunohistochemical results are extrapolated to professional football players, concussions result in no or minimal brain injury. Repeat impacts at higher velocity or with a heavier mass impactor cause extensive and distant diffuse axonal injury. Based on this model, the threshold for diffuse axonal injury is above even the most severe conditions for National Football League concussion.