title: Neuronal and glial changes in the brain resulting from explosive blast in an experimental model.
abstract: Mild traumatic brain injury (mTBI) is the signature injury in warfighters exposed to explosive blasts. The pathology underlying mTBI is poorly understood, as this condition is rarely fatal and thus postmortem brains are difficult to obtain for neuropathological studies. Here we report on studies of an experimental model with a gyrencephalic brain that is exposed to single and multiple explosive blast pressure waves. To determine injuries to the brain resulting from the primary blast, experimental conditions were controlled to eliminate any secondary or tertiary injury from blasts. We found small but significant levels of neuronal loss in the hippocampus, a brain area that is important for cognitive functions. Furthermore, neuronal loss increased with multiple blasts and the degree of neuronal injury worsened with time post-blast. This is consistent with our findings in the blast-exposed human brain based on magnetic resonance spectroscopic imaging. The studies on this experimental model thus confirm what has been presumed to be the case with the warfighter, namely that exposure to multiple blasts causes increased brain injury. Additionally, as in other studies of both explosive blast as well as closed head mTBI, we found astrocyte activation. Activated microglia were also prominent in white matter tracts, particularly in animals exposed to multiple blasts and at long post-blast intervals, even though injured axons (i.e. β-APP positive) were not found in these areas. Microglial activation appears to be a delayed response, though whether they may contribute to inflammation related injury mechanism at even longer post-blast times than we tested here, remains to be explored. Petechial hemorrhages or other gross signs of vascular injury were not observed in our study. These findings confirm the development of neuropathological changes due to blast exposure. The activation of astrocytes and microglia, cell types potentially involved in inflammatory processes, suggest an important area for future study.
authors.affiliation: Department of Comparative Medicine, Yale School of Medicine, New Haven, CT, USA.
authors.forename: James A
authors.initials: JA
authors.lastname: Goodrich
authors.affiliation: Department of Pathology, Yale School of Medicine, New Haven, CT, USA.
authors.forename: Jung H
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Department of Neurosurgery, Yale School of Medicine, 333 Cedar Street, New Haven, CT, 06520-8082, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Situ
authors.affiliation: Advanced Medical Training, McKinney, TX, USA.
authors.forename: Wesley
authors.initials: W
authors.lastname: Taylor
authors.affiliation: Advanced Medical Training, McKinney, TX, USA.
authors.forename: Ted
authors.initials: T
authors.lastname: Westmoreland
authors.affiliation: FD NeuroTechnologies Inc., Ellicott City, MD, USA.
authors.forename: Fu
authors.initials: F
authors.lastname: Du
authors.affiliation: ORA Inc, Fredericksburg, VA, USA.
authors.forename: Steven
authors.initials: S
authors.lastname: Parks
authors.affiliation: Department of Neurology, Edward Hébert School of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.
authors.forename: Geoffrey
authors.initials: G
authors.lastname: Ling
authors.affiliation: Department of Pathology, Yale School of Medicine, New Haven, CT, USA.
authors.forename: Jung Y
authors.initials: JY
authors.lastname: Hwang
authors.affiliation: Department of Neurosurgery, Yale School of Medicine, 333 Cedar Street, New Haven, CT, 06520-8082, USA.
authors.forename: Amedeo
authors.initials: A
authors.lastname: Rapuano
authors.affiliation: Department of Neurology, Edward Hébert School of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.|Integrated Services Group Inc., Potomac, MD, USA.
authors.forename: Faris A
authors.initials: FA
authors.lastname: Bandak
authors.affiliation: Department of Neurosurgery, Yale School of Medicine, 333 Cedar Street, New Haven, CT, 06520-8082, USA. nihal.delanerolle@yale.edu.
authors.forename: Nihal C
authors.initials: NC
authors.lastname: de Lanerolle
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000473:pathology*; D001753:Blast Injuries / Q000150:complications / Q000473:pathology*; D001921:Brain / Q000473:pathology*; D001930:Brain Injuries / Q000209:etiology / Q000473:pathology*; D002452:Cell Count; D004195:Disease Models, Animal; D008297:Male; D017628:Microglia / Q000473:pathology*; D009474:Neurons / Q000473:pathology*; D013552:Swine; D013556:Swine, Miniature