Rate of Neurodegeneration in the Mouse Controlled Cortical Impact Model Is Influenced by Impactor Tip Shape: Implications for Mechanistic and Therapeutic Studies
- 1 November 2011
- journal article
- research article
- Published by Mary Ann Liebert Inc in Journal of Neurotrauma
- Vol. 28 (11), 2245-2262
- https://doi.org/10.1089/neu.2010.1499
Abstract
Controlled cortical impact (CCI), one of the most common models of traumatic brain injury, is being increasingly used with mice for exploration of cell injury mechanisms and pre-clinical evaluation of therapeutic strategies. Although CCI brain injury was originally effected using an impactor with a rounded tip, the majority of studies with mouse CCI use a flat or beveled tip. Recent finite element modeling analyses demonstrate that tip geometry is a significant determinant of predicted cortical tissue strains in rat CCI, and that cell death is proportional to predicted tissue strains. In the current study, a three-dimensional finite element model of a C57BL/6J mouse brain predicted higher maximum principal strains during a simulated 1.0-mm, 3.5-m/s CCI injury with a flat tip when compared to a rounded tip. Consistent with this prediction, experimental CCI with a flat-tip impactor resulted in greater acute cortical hemorrhage and neuron loss in adult male C57BL/6J mice. The amount of neocortical tissue damage was equivalent for the two tip geometries at 9 days following injury, but the rate of neocortical neurodegeneration was markedly slower following CCI with a rounded-tip impactor, with damage reaching a plateau after 24 h as opposed to after 4 h for the flat tip. The flat-tip impactor was associated in general with more regional hippocampal neurodegeneration, especially at early time points such as 4 h. Impactor tip geometry did not have a notable effect on blood–brain barrier breakdown, traumatic axonal injury, or motor and cognitive dysfunction. Execution of CCI injury with a rounded-tip impactor is posited to provide a substantially enhanced temporal window for the study of cellular injury mechanisms and therapeutic intervention while maintaining critical aspects of the pathophysiological response to contusion brain injury.Keywords
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