A Novel Closed-Head Model of Mild Traumatic Brain Injury Using Focal Primary Overpressure Blast to the Cranium in Mice

作者:Guley Natalie H; Rogers Joshua T; Del Mar Nobel A; Deng Yunping; Islam Rafiqul M; D'Surney Lauren; Ferrell Jessica; Deng Bowei; Hines Beard Jessica; Bu Wei; Ren Huiling; Elberger Andrea J; Marchetta Jeffrey G; Rex Tonia S; Honig Marcia G; Reiner Anton*
来源:Journal of Neurotrauma, 2016, 33(4): 403-422.
DOI:10.1089/neu.2015.3886

摘要

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 7.5mm 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 25-40psi blast yields only slight motor deficits and brain damage. By contrast, a single 50-60psi 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.

  • 出版日期2016-2-15