title: Isolated primary blast alters neuronal function with minimal cell death in organotypic hippocampal slice cultures.
abstract: An increasing number of U.S. soldiers are diagnosed with traumatic brain injury (TBI) subsequent to exposure to blast. In the field, blast injury biomechanics are highly complex and multi-phasic. The pathobiology caused by exposure to some of these phases in isolation, such as penetrating or inertially driven injuries, has been investigated extensively. However, it is unclear whether the primary component of blast, a shock wave, is capable of causing pathology on its own. Previous in vivo studies in the rodent and pig have demonstrated that it is difficult to deliver a primary blast (i.e., shock wave only) without rapid head accelerations and potentially confounding effects of inertially driven TBI. We have previously developed a well-characterized shock tube and custom in vitro receiver for exposing organotypic hippocampal slice cultures to pure primary blast. In this study, isolated primary blast induced minimal hippocampal cell death (on average, below 14% in any region of interest), even for the most severe blasts tested (424 kPa peak pressure, 2.3 ms overpressure duration, and 248 kPa*ms impulse). In contrast, measures of neuronal function were significantly altered at much lower exposures (336 kPa, 0.84 ms, and 86.5 kPa*ms), indicating that functional changes occur at exposures below the threshold for cell death. This is the first study to investigate a tolerance for primary blast-induced brain cell death in response to a range of blast parameters and demonstrate functional deficits at subthreshold exposures for cell death.
authors.affiliation: 1 Department of Biomedical Engineering, Columbia University , New York, New York.
authors.forename: Gwen B
authors.initials: GB
authors.lastname: Effgen
authors.forename: Edward W
authors.initials: EW
authors.lastname: Vogel
authors.forename: Kimberly A
authors.initials: KA
authors.lastname: Lynch
authors.forename: Ayelet
authors.initials: A
authors.lastname: Lobel
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Hue
authors.forename: David F
authors.initials: DF
authors.lastname: Meaney
authors.forename: Cameron R Dale
authors.initials: CR
authors.lastname: Bass
authors.forename: Barclay
authors.initials: B
authors.lastname: Morrison
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001753:Blast Injuries / Q000473:pathology / Q000503:physiopathology*; D016923:Cell Death / Q000502:physiology; D006624:Hippocampus / Q000473:pathology / Q000502:physiology*; D009474:Neurons / Q000473:pathology / Q000502:physiology*; D009924:Organ Culture Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley
keywords: blast; hippocampus; in vitro; neuron; shock tube