Citation

Garman RH, Jenkins LW, Switzer RC, Bauman RA, Tong LC, Swauger PV, Parks S, Ritzel DV, Dixon CE, Clark R, Bayir H, Kagan V, Jackson E, Kochanek PM. J. Neurotrauma 2011; 28(6): 947-959.

Affiliation

University of Pittsburgh, Pathology, Pittsburgh, Pennsylvania, United States; vetpathol@cs.com.

Copyright

(Copyright © 2011, Mary Ann Liebert Publishers)

DOI

10.1089/neu.2010.1540

PMID

21449683

Abstract

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 35 pounds per square inch (PSI) nominal exposure (positive phase-duration ~4ms). Using an IACUC-approved protocol, isoflurane-anesthetized rats were placed in a steel wedge (to shield the body) 7 ft 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 wks post-blast. Neuropathologic evaluations were performed utilizing H&E, amino cupric silver, and a variety of immunohistochemical stains for APP, GFAP, 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, or 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 wks 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.

Language: en