title: Blood-brain barrier dysfunction after primary blast injury in vitro.
abstract: The incidence of blast-induced traumatic brain injury (bTBI) has increased substantially in recent military conflicts. However, the consequences of bTBI on the blood-brain barrier (BBB), a specialized cerebrovascular structure essential for brain homeostasis, remain unknown. In this study, we utilized a shock tube driven by compressed gas to generate operationally relevant, ideal pressure profiles consistent with improvised explosive devices (IEDs). By multiple measures, the barrier function of an in vitro BBB model was disrupted following exposure to a range of controlled blast loading conditions. Trans-endothelial electrical resistance (TEER) decreased acutely in a dose-dependent manner that was most strongly correlated with impulse, as opposed to peak overpressure or duration. Significantly increased hydraulic conductivity and solute permeability post-injury further confirmed acute alterations in barrier function. Compromised ZO-1 immunostaining identified a structural basis for BBB breakdown. After blast exposure, TEER remained significantly depressed 2 days post-injury, followed by spontaneous recovery to pre-injury control levels at day 3. This study is the first to report immediate disruption of an in vitro BBB model following primary blast exposure, which may be important for the development of novel helmet designs to help mitigate the effects of blast on the BBB.
authors.affiliation: 1 Department of Biomedical Engineering, Columbia University , New York, New York.
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Hue
authors.forename: Siqi
authors.initials: S
authors.lastname: Cao
authors.forename: Syed F
authors.initials: SF
authors.lastname: Haider
authors.forename: Kiet V
authors.initials: KV
authors.lastname: Vo
authors.forename: Gwen B
authors.initials: GB
authors.lastname: Effgen
authors.forename: Edward
authors.initials: E
authors.lastname: Vogel
authors.forename: Matthew B
authors.initials: MB
authors.lastname: Panzer
authors.forename: Cameron R Dale
authors.initials: CR
authors.lastname: Bass
authors.forename: David F
authors.initials: DF
authors.lastname: Meaney
authors.forename: Barclay
authors.initials: B
authors.lastname: Morrison
mesh_terms: D000818:Animals; D001696:Biomechanical Phenomena; D001753:Blast Injuries / Q000503:physiopathology*; D001812:Blood-Brain Barrier / Q000293:injuries* / Q000503:physiopathology*; D001930:Brain Injuries / Q000503:physiopathology*; D002199:Capillary Permeability; D002478:Cells, Cultured; D017097:Electric Impedance; D004848:Epithelium / Q000378:metabolism / Q000503:physiopathology; D007150:Immunohistochemistry; D051379:Mice