title: A Novel Closed-Head Model of Mild Traumatic Brain Injury Using Focal Primary Overpressure Blast to the Cranium in Mice.
abstract: Mild traumatic brain injury (TBI) from focal head impact is the most common form of TBI in humans. Animal models, however, typically use direct impact to the exposed dura or skull, or blast to the entire head. We present a detailed characterization of a novel overpressure blast system to create focal closed-head mild TBI in mice. A high-pressure air pulse limited to a 7.5 mm diameter area on the left side of the head overlying the forebrain is delivered to anesthetized mice. The mouse eyes and ears are shielded, and its head and body are cushioned to minimize movement. This approach creates mild TBI by a pressure wave that acts on the brain, with minimal accompanying head acceleration-deceleration. A single 20-psi blast yields no functional deficits or brain injury, while a single 25-40 psi blast yields only slight motor deficits and brain damage. By contrast, a single 50-60 psi blast produces significant visual, motor, and neuropsychiatric impairments and axonal damage and microglial activation in major fiber tracts, but no contusive brain injury. This model thus reproduces the widespread axonal injury and functional impairments characteristic of closed-head mild TBI, without the complications of systemic or ocular blast effects or head acceleration that typically occur in other blast or impact models of closed-skull mild TBI. Accordingly, our model provides a simple way to examine the biomechanics, pathophysiology, and functional deficits that result from TBI and can serve as a reliable platform for testing therapies that reduce brain pathology and deficits.
authors.affiliation: 1 Department of Anatomy and Neurobiology, The University of Tennessee Health Science Center , Memphis, Tennessee.
authors.forename: Natalie H
authors.initials: NH
authors.lastname: Guley
authors.affiliation: 1 Department of Anatomy and Neurobiology, The University of Tennessee Health Science Center , Memphis, Tennessee.
authors.forename: Joshua T
authors.initials: JT
authors.lastname: Rogers
authors.affiliation: 1 Department of Anatomy and Neurobiology, The University of Tennessee Health Science Center , Memphis, Tennessee.
authors.forename: Nobel A
authors.initials: NA
authors.lastname: Del Mar
authors.affiliation: 1 Department of Anatomy and Neurobiology, The University of Tennessee Health Science Center , Memphis, Tennessee.
authors.forename: Yunping
authors.initials: Y
authors.lastname: Deng
authors.affiliation: 1 Department of Anatomy and Neurobiology, The University of Tennessee Health Science Center , Memphis, Tennessee.|5 Department of Anatomy and Histology, Bangladesh Agricultural University , Mymensingh, Bangladesh .
authors.forename: Rafiqul M
authors.initials: RM
authors.lastname: Islam
authors.affiliation: 1 Department of Anatomy and Neurobiology, The University of Tennessee Health Science Center , Memphis, Tennessee.|2 Department of Ophthalmology, The University of Tennessee Health Science Center , Memphis, Tennessee.
authors.forename: Lauren
authors.initials: L
authors.lastname: D'Surney
authors.affiliation: 1 Department of Anatomy and Neurobiology, The University of Tennessee Health Science Center , Memphis, Tennessee.
authors.forename: Jessica
authors.initials: J
authors.lastname: Ferrell
authors.affiliation: 1 Department of Anatomy and Neurobiology, The University of Tennessee Health Science Center , Memphis, Tennessee.
authors.forename: Bowei
authors.initials: B
authors.lastname: Deng
authors.affiliation: 2 Department of Ophthalmology, The University of Tennessee Health Science Center , Memphis, Tennessee.|3 Department of Ophthalmology and Visual Sciences, Vanderbilt University , Nashville, Tennessee.
authors.forename: Jessica
authors.initials: J
authors.lastname: Hines-Beard
authors.affiliation: 1 Department of Anatomy and Neurobiology, The University of Tennessee Health Science Center , Memphis, Tennessee.
authors.forename: Wei
authors.initials: W
authors.lastname: Bu
authors.affiliation: 1 Department of Anatomy and Neurobiology, The University of Tennessee Health Science Center , Memphis, Tennessee.
authors.forename: Huiling
authors.initials: H
authors.lastname: Ren
authors.affiliation: 1 Department of Anatomy and Neurobiology, The University of Tennessee Health Science Center , Memphis, Tennessee.
authors.forename: Andrea J
authors.initials: AJ
authors.lastname: Elberger
authors.affiliation: 4 Department of Mechanical Engineering, University of Memphis , Memphis, Tennessee.
authors.forename: Jeffrey G
authors.initials: JG
authors.lastname: Marchetta
authors.affiliation: 2 Department of Ophthalmology, The University of Tennessee Health Science Center , Memphis, Tennessee.|3 Department of Ophthalmology and Visual Sciences, Vanderbilt University , Nashville, Tennessee.
authors.forename: Tonia S
authors.initials: TS
authors.lastname: Rex
authors.affiliation: 1 Department of Anatomy and Neurobiology, The University of Tennessee Health Science Center , Memphis, Tennessee.
authors.forename: Marcia G
authors.initials: MG
authors.lastname: Honig
authors.affiliation: 1 Department of Anatomy and Neurobiology, The University of Tennessee Health Science Center , Memphis, Tennessee.|2 Department of Ophthalmology, The University of Tennessee Health Science Center , Memphis, Tennessee.
authors.forename: Anton
authors.initials: A
authors.lastname: Reiner
mesh_terms: D000399:Air Pressure; D000818:Animals; D001924:Brain Concussion / Q000209:etiology / Q000473:pathology* / Q000503:physiopathology*; D004195:Disease Models, Animal; D005107:Explosions; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D012886:Skull / Q000293:injuries*
keywords: axonal injury; mild TBI; motor deficits; overpressure blast; visual deficits