A Novel <em>In Vitro</em> Model of Blast Traumatic Brain Injury

Abstract

Traumatic brain injury is a leading cause of death and disability in military and civilian populations. Blast traumatic brain injury results from the detonation of explosive devices, however, the mechanisms that underlie the brain damage resulting from blast overpressure exposure are not entirely understood and are believed to be unique to this type of brain injury. Preclinical models are crucial tools that contribute to better understand blast-induced brain injury. A novel in vitro blast TBI model was developed using an open-ended shock tube to simulate real-life open-field blast waves modelled by the Friedlander waveform. C57BL/6N mouse organotypic hippocampal slice cultures were exposed to single shock waves and the development of injury was characterized up to 72 h using propidium iodide, a well-established fluorescent marker of cell damage that only penetrates cells with compromised cellular membranes. Propidium iodide fluorescence was significantly higher in the slices exposed to a blast wave when compared with sham slices throughout the duration of the protocol. The brain tissue injury is very reproducible and proportional to the peak overpressure of the shock wave applied.

Xenon treatment after severe traumatic brain injury improves locomotor outcome, reduces acute neuronal loss and enhances early beneficial neuroinflammation: a randomized, blinded, controlled animal study

“…Xenon has been shown to be neuroprotective using in vitro and in vivo models of ischemic brain injury [4,[13][14][15][16][17][18][19], and a recent two-center clinical trial of xenon for brain injury after out-of-hospital cardiac arrest showed evidence of reduced cerebral white matter damage [20]. Until recently, the efficacy of xenon as a neuroprotectant in TBI has been limited to simple in vitro models [21][22][23][24]. We recently demonstrated for the first time in an animal model that xenon is neuroprotective following moderate TBI in mice [25].…”

Noble gas neuroprotection: xenon and argon protect against hypoxic–ischaemic injury in rat hippocampus in vitro via distinct mechanisms

“…This preparation retains a variety of cell types (e.g. different types of neurones and glia) with cellular organisation and synaptic connectivity similar to in vivo ,34, 35 and is widely used as an intermediate between dissociated cell cultures and whole-animal models 20, 24, 26, 28, 36, 37, 38, 39, 40. We chose 30 min as the duration of OGD because we previously showed that this produced a reliable and robust injury 24 .…”

“…Animals were checked at least once daily. Organotypic hippocampal slice cultures were prepared as described24, 26, 28, 29 from male and female 7-day-old C57BL/6 mouse pups (Harlan Ltd, Bicester, Oxfordshire, UK). Briefly, after euthanasia, brains were removed and placed in ice-cold ‘preparation’ medium that contained Gey's balanced salt solution, 33 mM d -glucose (Fisher Scientific, Loughborough, Leicestershire, UK) and 1% antibiotic–antimycotic suspension.…”

Current ex vivo and in vitro approaches to uncovering mechanisms of neurological dysfunction after traumatic brain injury

“…Specifically, blast (29,30) and stretch (31)(32)(33) have been applied to organotypic slices (B) and neuronal stretch (41-43) and axotomy (44-46) injuries have been applied to primary neuronal cultures (C). The only non-invasive human neuronal investigations involve the use of human induced pluripotent stem cells (hiPSCs) (D).…”