TEMPORAL AND REGIONAL PATTERNS OF AXONAL DAMAGE FOLLOWING TRAUMATIC BRAIN INJURY - A BETA-AMYLOID PRECURSOR PROTEIN IMMUNOCYTOCHEMICAL STUDY IN RATS

Diffuse axonal injury (DAI) is an important consequence of human head trauma. This experimental investigation utilized the immunocytochemica l visualization of beta-amyloid precursor protein (beta-APP) to docume nt regional patterns of axonal injury after traumatic brain injury (TB I) and to determine the importance of injury severity on the magnitude of axonal damage. Rats underwent moderate (1.84-2.11 atm) or severe ( 2.38-2.52 atm) parasagittal fluid-percussion (F-P) brain injury or sha m procedures. At 1, 3, 7 or 30 days after TBI, rats were perfusion-fix ed and sections immunostained for the visualization of beta-APP. A reg ionally specific axonal response to TBI was documented after moderate F-P injury. Within the dorsolateral striatum, an early increase in bet a-APP-positive axonal profiles at 24 hours (h) was followed by a signi ficant decline at subsequent survival periods. In contrast, the freque ncy of reactive profiles was initially low within the thalamus, but in creased significantly by day 7. Within the external capsule at the inj ury epicenter, numbers of immunoreactive axons increased significantly at 24 h and remained elevated throughout the subsequent survival peri ods. At multiple periods after TBI, selective cortical and thalamic ne urons displayed increased staining of the perikarya. A significant inc rease in the overall frequency of beta-APP profiles was documented in the severe vs moderately injured rats at 72 h after TBI. These data in dicate that parasagittal F-P brain injury (a) results in widespread ax onal damage, (b) that axonal damage includes both reversible and delay ed patterns, and (c) that injury severity is an important factor in de termining the severity of the axonal response to TBI.