title: Neuroinflammation in primary blast neurotrauma: Time course and prevention by torso shielding.
abstract: Mechanisms of primary blast injury caused by overpressure are not fully understood. In particular, the presence and time course of neuroinflammation are unknown and so are the signatures of reactive inflammatory cells, especially the neuroprotective versus injurious roles of microglia. In general, chronic microglial activation in the injured brain suggests a pro-degenerative role for these reactive cells. In this study, we investigated the temporal dynamics of microglial activation in the brain of mice exposed to mild-moderate blast in a shock tube. Because, in our previous work, we had found that torso shielding with rigid Plexiglas attenuates traumatic axonal injury in the brain, we also evaluated neuroinflammatory microglial responses in animals with torso protection at 7 days post blast injury. Because of the prominent involvement of the visual system in blast TBI in rodents, activated microglial cells were counted in the optic tract at various time points post-injury with stereological methods. Cell counts (activated microglial cell densities) from subjects exposed to blast TBI were compared with counts from corresponding sham animals. We found that mild-moderate blast injury causes focal activation of microglia in certain white matter tracts, including the visual pathway. In the optic tract, the density of activated microglial profiles gradually intensified from 3 to 15 days post-injury and then became attenuated at 30 days. Torso protection significantly reduced microglial activation at 7 days. These findings shed light into mechanisms of primary blast neurotrauma and may suggest novel diagnostic and monitoring methods for patients. They leave open the question of whether microglial activation post blast is protective or detrimental, although response is time limited. Finally, our findings confirm the protective role of torso shielding and stress the importance of improved or optimized body gear for warfighters or other individuals at risk for blast exposure.
authors.affiliation: Division of Neuropathology, Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. Electronic address: lxu9@jhmi.edu.
authors.forename: Leyan
authors.initials: L
authors.lastname: Xu
authors.affiliation: National Security Technology, Johns Hopkins University Applied Physics Laboratory, Laurel, MD 20723, USA; Department of Neurology, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. Electronic address: mschae11@jhmi.edu.
authors.forename: Michele L
authors.initials: ML
authors.lastname: Schaefer
authors.affiliation: National Security Technology, Johns Hopkins University Applied Physics Laboratory, Laurel, MD 20723, USA; Department of Neurology, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. Electronic address: raleigh@bu.edu.
authors.forename: Raleigh M
authors.initials: RM
authors.lastname: Linville
authors.affiliation: Division of Neuropathology, Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Neurology, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. Electronic address: ayushi1@umbc.edu.
authors.forename: Ayushi
authors.initials: A
authors.lastname: Aggarwal
authors.affiliation: National Security Technology, Johns Hopkins University Applied Physics Laboratory, Laurel, MD 20723, USA; Department of Neurology, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. Electronic address: wmbuguiro@gmail.com.
authors.forename: Wangui
authors.initials: W
authors.lastname: Mbuguiro
authors.affiliation: National Security Technology, Johns Hopkins University Applied Physics Laboratory, Laurel, MD 20723, USA; Department of Neurology, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. Electronic address: Brock.Wester@jhuapl.edu.
authors.forename: Brock A
authors.initials: BA
authors.lastname: Wester
authors.affiliation: Division of Neuropathology, Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; National Security Technology, Johns Hopkins University Applied Physics Laboratory, Laurel, MD 20723, USA; Department of Psychiatry and Behavioral Sciences, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. Electronic address: koliat@jhmi.edu.
authors.forename: Vassilis E
authors.initials: VE
authors.lastname: Koliatsos
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D001753:Blast Injuries / Q000150:complications*; D002135:Calcium-Binding Proteins / Q000378:metabolism; D004195:Disease Models, Animal; D004660:Encephalitis / Q000209:etiology* / Q000517:prevention & control*; D051664:Kv1.3 Potassium Channel / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008840:Microfilament Proteins / Q000378:metabolism; D017628:Microglia / Q000473:pathology; D065866:Optic Tract / Q000473:pathology; D011482:Protective Devices; D013997:Time Factors; D060726:Torso / Q000502:physiology*; D000097382:CD68 Molecule
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D002135:Calcium-Binding Proteins; D051664:Kv1.3 Potassium Channel; D008840:Microfilament Proteins; C491049:Aif1 protein, mouse; C067980:CD68 antigen, human; D000097382:CD68 Molecule
keywords: Microglia; Neurotrauma; Optic tract; Primary blast injury; Traumatic axonal injury