Stemper Brian D, Shah Alok S, Pintar Frank A, McCrea Michael, Kurpad Shekar N, Glavaski-Joksimovic Aleksandra, Olsen Christopher, Budde Matthew D
Department of Neurosurgery, Medical College of Wisconsin, Clement J. Zablocki Veterans Affairs Medical Center, Milwaukee, WI, USA,
Ann Biomed Eng. 2015 May;43(5):1071-88. doi: 10.1007/s10439-014-1171-9. Epub 2014 Oct 25.
A majority of traumatic brain injuries (TBI) in motor vehicle crashes and sporting environments are mild and caused by high-rate acceleration of the head. For injuries caused by rotational acceleration, both magnitude and duration of the acceleration pulse were shown to influence injury outcomes. This study incorporated a unique rodent model of rotational acceleration-induced mild TBI (mTBI) to quantify independent effects of magnitude and duration on behavioral and neuroimaging outcomes. Ninety-two Sprague-Dawley rats were exposed to head rotational acceleration at peak magnitudes of 214 or 350 krad/s(2) and acceleration pulse durations of 1.6 or 3.4 ms in a full factorial design. Rats underwent a series of behavioral tests including the Composite Neuroscore (CN), Elevated Plus Maze (EPM), and Morris Water Maze (MWM). Ex vivo diffusion tensor imaging (DTI) of the fixed brains was conducted to assess the effects of rotational injury on brain microstructure as revealed by the parameter fractional anisotropy (FA). While the injury did not cause significant locomotor or cognitive deficits measured with the CN and MWM, respectively, a main effect of duration was consistently observed for the EPM. Increased duration caused significantly greater activity and exploratory behaviors measured as open arm time and number of arm changes. DTI demonstrated significant effects of both magnitude and duration, with the FA of the amygdala related to both the magnitude and duration. Increased duration also caused FA changes at the interface of gray and white matter. Collectively, the findings demonstrate that the consequences of rotational acceleration mTBI were more closely associated with duration of the rotational acceleration impulse, which is often neglected as an independent factor, and highlight the need for animal models of TBI with strong biomechanical foundations to associate behavioral outcomes with brain microstructure.
在机动车碰撞和体育环境中，大多数创伤性脑损伤（TBI）为轻度损伤，由头部的高速加速所致。对于旋转加速导致的损伤，加速脉冲的幅度和持续时间均显示会影响损伤结果。本研究采用了一种独特的旋转加速诱导轻度创伤性脑损伤（mTBI）的啮齿动物模型，以量化幅度和持续时间对行为及神经影像学结果的独立影响。采用完全析因设计，将92只Sprague-Dawley大鼠暴露于峰值幅度为214或350 krad/s(2) 、加速脉冲持续时间为1.6或3.4 ms的头部旋转加速中。大鼠接受了一系列行为测试，包括综合神经评分（CN）、高架十字迷宫（EPM）和莫里斯水迷宫（MWM）。对固定大脑进行离体扩散张量成像（DTI），以通过分数各向异性（FA）参数评估旋转损伤对脑微结构的影响。虽然损伤分别未导致用CN和MWM测量的明显运动或认知缺陷，但在EPM中持续观察到持续时间的主要影响。持续时间增加导致以开放臂时间和臂变化次数衡量的活动和探索行为显著增加。DTI显示幅度和持续时间均有显著影响，杏仁核的FA与幅度和持续时间均相关。持续时间增加还导致灰质和白质界面处的FA变化。总体而言，研究结果表明，旋转加速mTBI的后果与旋转加速脉冲的持续时间更密切相关，而旋转加速脉冲持续时间作为一个独立因素常常被忽视，这突出了需要具有强大生物力学基础的TBI动物模型，以便将行为结果与脑微结构联系起来。
