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首页> 外文期刊>Journal of neurotrauma >Rate of neurodegeneration in the mouse controlled cortical impact model is influenced by impactor tip shape: implications for mechanistic and therapeutic studies.
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Rate of neurodegeneration in the mouse controlled cortical impact model is influenced by impactor tip shape: implications for mechanistic and therapeutic studies.

机译：小鼠控制的皮质撞击模型中神经退行性改变的速度受撞击器尖端形状的影响：对机械和治疗研究的意义。

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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.
机译：受控皮质撞击（CCI）是颅脑外伤最常见的模型之一，目前正越来越多地与小鼠一起使用，以探索细胞损伤机制和临床前评估治疗策略。尽管CCI脑损伤最初是使用带有圆形尖端的撞击器来实现的，但大多数使用鼠标CCI的研究都使用了扁平或斜角的尖端。最近的有限元建模分析表明，尖端几何形状是大鼠CCI中预测的皮质组织应变的重要决定因素，并且细胞死亡与预测的组织应变成比例。在当前的研究中，C57BL / 6J小鼠大脑的三维有限元模型预测，与圆形尖端相比，在模拟的1.0mm，3.5m / s CCI损伤期间，平坦尖端的最大主应变更高。与该预测一致，具有平顶冲击器的实验性CCI在成年雄性C57BL / 6J小鼠中导致更大的急性皮质出血和神经​​元丢失。损伤后第9天，两个尖端几何形状的新皮质组织损伤量是相等的，但是CCI后使用圆尖端冲击器后，新皮质神经退行性变的速度明显减慢，损伤在24小时后达到平稳，而不是在24小时后达到平稳。平头4？h。平顶冲击器通常与更多的区域性海马神经退行性变有关，尤其是在诸如4？h的早期时间点。撞击器尖端的几何形状对血脑屏障的破坏，轴突创伤，运动和认知功能障碍没有显着影响。提出了使用圆头撞击器执行CCI损伤的方法，可为研究细胞损伤机制和治疗干预提供显着增强的时间窗口，同时保持对挫伤性脑损伤的病理生理反应的关键方面。

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