Blast-induced
traumatic brain injury (TBI) is the signature insult in combat casualty care. Survival with neurological damage from otherwise lethal blast exposures has become possible with body armor use. We characterized the neuropathologic alterations produced by a single blast exposure in rats using a
helium-driven
shock tube to generate a nominal exposure of 35 pounds per square inch (PSI) (positive phase duration ∼ 4 msec). Using an IACUC-approved protocol,
isoflurane-anesthetized rats were placed in a steel wedge (to shield the body) 7 feet inside the end of the tube. The left side faced the blast wave (with head-only exposure); the wedge apex focused a Mach stem onto the rat's head. The insult produced ∼ 25% mortality (due to impact
apnea). Surviving and
sham rats were perfusion-fixed at 24 h, 72 h, or 2 weeks post-blast. Neuropathologic evaluations were performed utilizing
hematoxylin and
eosin, amino cupric
silver, and a variety of immunohistochemical stains for
amyloid precursor
protein (APP),
glial fibrillary acidic protein (GFAP), ionized
calcium-binding adapter molecule 1 (Iba1), ED1, and rat
IgG. Multifocal axonal degeneration, as evidenced by staining with amino cupric
silver, was present in all blast-exposed rats at all time points. Deep cerebellar and brainstem white matter tracts were most heavily stained with amino cupric
silver, with the morphologic staining patterns suggesting a process of
diffuse axonal injury.
Silver-stained sections revealed mild multifocal neuronal death at 24 h and 72 h. GFAP, ED1, and Iba1 staining were not prominently increased, although small numbers of reactive microglia were seen within areas of neuronal death. Increased blood-brain barrier permeability (as measured by
IgG staining) was seen at 24 h and primarily affected the contralateral cortex. Axonal injury was the most prominent feature during the initial 2 weeks following blast exposure, although degeneration of other neuronal processes was also present. Strikingly,
silver staining revealed otherwise undetected abnormalities, and therefore represents a recommended outcome measure in future studies of blast TBI.