title: Primary blast injury causes cognitive impairments and hippocampal circuit alterations.
abstract: Blast-induced traumatic brain injury (bTBI) and its long term consequences are a major health concern among veterans. Despite recent work enhancing our knowledge about bTBI, very little is known about the contribution of the blast wave alone to the observed sequelae. Herein, we isolated its contribution in a mouse model by constraining the animals' heads during exposure to a shockwave (primary blast). Our results show that exposure to primary blast alone results in changes in hippocampus-dependent behaviors that correspond with electrophysiological changes in area CA1 and are accompanied by reactive gliosis. Specifically, five days after exposure, behavior in an open field and performance in a spatial object recognition (SOR) task were significantly different from sham. Network electrophysiology, also performed five days after injury, demonstrated a significant decrease in excitability and increase in inhibitory tone. Immunohistochemistry for GFAP and Iba1 performed ten days after injury showed a significant increase in staining. Interestingly, a threefold increase in the impulse of the primary blast wave did not exacerbate these measures. However, we observed a significant reduction in the contribution of the NMDA receptors to the field EPSP at the highest blast exposure level. Our results emphasize the need to account for the effects of primary blast loading when studying the sequelae of bTBI.
authors.affiliation: Department of Bioengineering(1), University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Matthew
authors.initials: M
authors.lastname: Beamer
authors.affiliation: Department of Bioengineering(1), University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Shanti R
authors.initials: SR
authors.lastname: Tummala
authors.affiliation: Department of Bioengineering(1), University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: David
authors.initials: D
authors.lastname: Gullotti
authors.affiliation: Department of Bioengineering(1), University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Catherine
authors.initials: C
authors.lastname: Kopil
authors.affiliation: Department of Bioengineering(1), University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Samuel
authors.initials: S
authors.lastname: Gorka
authors.affiliation: Department of Biology, University of Pennsylvania, Philadelphia, PA, USA.
authors.lastname: Ted Abel
authors.affiliation: Department of Biomedical Engineering, Duke University, Durham, NC, USA.
authors.forename: Cameron R Dale
authors.initials: CR
authors.lastname: Bass
authors.affiliation: Department of Biomedical Engineering, Columbia University, New York, NY, USA.
authors.forename: Barclay
authors.initials: B
authors.lastname: Morrison
authors.affiliation: Department of Anesthesiology and Critical Care Medicine, University of Pennsylvania, Philadelphia, PA, USA; Division of Critical Care Medicine, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
authors.forename: Akiva S
authors.initials: AS
authors.lastname: Cohen
authors.affiliation: Department of Bioengineering(1), University of Pennsylvania, Philadelphia, PA, USA; Department of Neurosurgery, University of Pennsylvania, Philadelphia, PA, USA. Electronic address: dmeaney@seas.upenn.edu.
authors.forename: David F
authors.initials: DF
authors.lastname: Meaney
mesh_terms: D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D000818:Animals; D001696:Biomechanical Phenomena; D001930:Brain Injuries / Q000150:complications* / Q000473:pathology*; D002135:Calcium-Binding Proteins / Q000378:metabolism; D003072:Cognition Disorders / Q000209:etiology*; D004195:Disease Models, Animal; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005106:Exploratory Behavior / Q000502:physiology; D005239:Fear / Q000523:psychology; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006624:Hippocampus / Q000473:pathology*; D008297:Male; D018782:Maze Learning; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D008840:Microfilament Proteins / Q000378:metabolism; D009043:Motor Activity / Q000502:physiology; D009415:Nerve Net / Q000473:pathology*; D045442:Rotarod Performance Test; D013997:Time Factors
chemical_list: C491049:Aif1 protein, mouse; D002135:Calcium-Binding Proteins; D018691:Excitatory Amino Acid Antagonists; D005904:Glial Fibrillary Acidic Protein; D008840:Microfilament Proteins; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione
keywords: Blast induced traumatic brain injury; Blood-brain barrier; Concussion