title: Time Course and Size of Blood-Brain Barrier Opening in a Mouse Model of Blast-Induced Traumatic Brain Injury.
abstract: An increasing number of studies have reported blood-brain barrier (BBB) dysfunction after blast-induced traumatic brain injury (bTBI). Despite this evidence, there is limited quantitative understanding of the extent of BBB opening and the time course of damage after blast injury. In addition, many studies do not report kinematic parameters of head motion, making it difficult to separate contributions of primary and tertiary blast-loading. Detailed characterization of blast-induced BBB damage may hold important implications for serum constituents that may potentially cross the compromised barrier and contribute to neurotoxicity, neuroinflammation, and persistent neurologic deficits. Using an in vivo bTBI model, systemic administration of sodium fluorescein (NaFl; 376 Da), Evans blue (EB; 69 kDa when bound to serum albumin), and dextrans (3-500 kDa) was used to estimate the pore size of BBB opening and the time required for recovery. Exposure to blast with 272 ± 6 kPa peak overpressure, 0.69 ± 0.01 ms duration, and 65 ± 1 kPa*ms impulse resulted in significant acute extravasation of NaFl, 3 kDa dextran, and EB. However, there was no significant acute extravasation of 70 kDa or 500 kDa dextrans, and minimal to no extravasation of NaFl, dextrans, or EB 1 day after exposure. This study presents a detailed analysis of the time course and pore size of BBB opening after bTBI, supported by a characterization of kinematic parameters associated with blast-induced head motion.
authors.affiliation: 1 Department of Biomedical Engineering, Columbia University , New York, New York.
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Hue
authors.affiliation: 1 Department of Biomedical Engineering, Columbia University , New York, New York.
authors.forename: Frances S
authors.initials: FS
authors.lastname: Cho
authors.affiliation: 1 Department of Biomedical Engineering, Columbia University , New York, New York.
authors.forename: Siqi
authors.initials: S
authors.lastname: Cao
authors.affiliation: 2 Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University , New York, New York.
authors.forename: Russell E
authors.initials: RE
authors.lastname: Nicholls
authors.affiliation: 1 Department of Biomedical Engineering, Columbia University , New York, New York.
authors.forename: Edward W
authors.initials: EW
authors.lastname: Vogel Iii
authors.affiliation: 1 Department of Biomedical Engineering, Columbia University , New York, New York.
authors.forename: Cosmas
authors.initials: C
authors.lastname: Sibindi
authors.affiliation: 2 Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University , New York, New York.
authors.forename: Ottavio
authors.initials: O
authors.lastname: Arancio
authors.affiliation: 3 Department of Biomedical Engineering, Duke University , Durham, North Carolina.
authors.forename: Cameron R
authors.initials: CR
authors.lastname: Dale Bass
authors.affiliation: 4 Department of Bioengineering, University of Pennsylvania , Philadelphia, Pennsylvania.
authors.forename: David F
authors.initials: DF
authors.lastname: Meaney
authors.affiliation: 1 Department of Biomedical Engineering, Columbia University , New York, New York.
authors.forename: Barclay
authors.initials: B
authors.lastname: Morrison Iii
mesh_terms: D000818:Animals; D001753:Blast Injuries / Q000150:complications*; D001812:Blood-Brain Barrier / Q000293:injuries* / Q000503:physiopathology*; D000070642:Brain Injuries, Traumatic / Q000150:complications*; D004195:Disease Models, Animal; D005260:Female; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL
keywords: blast injury; blood–brain barrier; dextran; shock tube; traumatic brain injury