Characterization of the Jet-Flow Overpressure Model of Traumatic Brain Injury in Mice

Abstract

The jet-flow overpressure chamber (OPC) has been previously reported as a model of blast-mediated traumatic brain injury (bTBI). However, rigorous characterization of the features of this injury apparatus shows that it fails to recapitulate exposure to an isolated blast wave. Through combined experimental and computational modeling analysis of gas-dynamic flow conditions, we show here that the jet-flow OPC produces a collimated high-speed jet flow with extreme dynamic pressure that delivers a severe compressive impulse. Variable rupture dynamics of the diaphragm through which the jet flow originates also generate a weak and infrequent shock front. In addition, there is a component of acceleration-deceleration injury to the head as it is agitated in the headrest. Although not a faithful model of free-field blast exposure, the jet-flow OPC produces a complex multi-modal model of TBI that can be useful in laboratory investigation of putative TBI therapies and fundamental neurophysiological processes after brain injury.

Longitudinal in vivo monitoring of axonal degeneration after brain injury

“…This generates a reproducible pattern of axonal degeneration, cognitive impairment, blood-brain barrier disruption, systemic metabolic alterations, and blood biomarkers that reliably mimic human TBI. 30 Following 2–3 baseline (pre-TBI) axonal activity recordings, mice were randomly assigned to 2 groups (3 mice/group): (1) TBI and (2) sham injury (control), in which mice were subjected to the same procedure except that the overpressure chamber was not activated. Post-TBI and sham injury recordings were conducted once per week over 7 weeks for all groups, starting 3 days after TBI or sham injury ( Figure S1 A).…”

Longitudinal in vivo monitoring of axonal integrity after brain injury

“…In this TBI model, an overpressure chamber delivers global concussion, acceleration/deceleration injury, and early blast wave exposure in an isolated manner to the head of an anesthetized mouse. This generates a reproducible pattern of axonal degeneration, cognitive impairment, blood-brain barrier disruption, systemic metabolic alterations, and blood biomarkers that reliably mimic human TBI 38 . Following 2-3 baseline (pre-TBI) axonal activity recordings, 9 mice were randomly assigned to three groups: 1) TBI, 2) TBI treatment, in which mice received TBI and daily P7C3-A20 starting 24 hours after injury, and 3) sham injury (control), in which mice were subjected to sham-TBI.…”

Increased Risk of Aging-Related Neurodegenerative Disease after Traumatic Brain Injury

“…These 4 distinct rodent models of TBI mimic different aspects of clinical TBI in people, with the first three modeling mechanical head trauma and the pure blast model entailing isolated exposure to a blast wave. To model the multimodal nature of most forms of human TBI, we recently characterized an additional rodent model of TBI that uses an overpressure chamber to deliver precise and reproducible aspects of global concussion, acceleration/deceleration injury, and early blast wave exposure without the need for surgery [ 24 ]. This model of multimodal TBI initiates acute axonal degeneration and BBB damage that persists chronically and progresses to neuronal cell death and behavioral alterations related to human neuropsychiatric impairment, with metabolomic changes in the blood that mimic changes seen in human TBI patients [ 25 , 26 , 27 , 28 , 29 , 30 , 31 ].…”