Lateral Fluid Percussion: Model of Traumatic Brain Injury in Mice
Lateral Fluid Percussion: Model of Traumatic Brain Injury in Mice
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DOI：
10.3791/3063
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发表时间：
2011-08-01
影响因子：
1.2
通讯作者：
Thakker-Varia, Smita
中科院分区：
文献类型：
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作者：
Alder, Janet;Fujioka, Wendy;Thakker-Varia, Smita
随着人们对导致发病率和死亡率的头部损伤的认识不断提高，创伤性脑损伤(TBI)的研究获得了新的动力。基于颅脑损伤后原发损伤的性质，导致复杂和不同的继发后果，继而是再生过程(1，2)。原发损伤可由颅骨骨折对大脑的直接挫伤或由于运动导致脑部移位的组织的剪切和拉伸引起(3，4)。由此产生的血肿和撕裂导致血管反应(3，5)，白质的形态和功能损害导致弥漫性轴突损伤(6-8)。在大脑中常见的其他继发性变化是水肿和颅内压升高(9)。颅脑损伤后，涉及兴奋性神经递质、免疫介质和氧自由基释放的生化和生理通路发生微观变化(10-12)，最终导致长期的神经残疾(13，14)。因此，选择合适的动物模型，使其在人类和啮齿动物中呈现相似的细胞和分子事件，对于研究损伤和修复的机制至关重要。各种脑损伤实验模型已经发展起来，以再现在人类中观察到的脑损伤的各个方面，其中三种特定的模型被广泛地适应于啮齿动物：液体撞击、皮质撞击和体重下降/撞击加速(1)。流体冲击装置通过对完整的硬脑膜施加短暂的流体压力脉冲，通过开颅手术产生损伤。这种脉冲是由钟摆撞击储液器的活塞而产生的。冲击产生神经组织的短暂移位和变形(1，15)。相反，皮质撞击伤通过气动压力下的刚性撞击器将机械能传递给完整的硬脑膜(16，17)。重量下降/撞击模型的特征是具有特定质量的杆落在封闭的头骨(18)上。在各种颅脑损伤模型中，LFP是评估混合性局灶性和弥漫性脑损伤最成熟、最常用的模型(19)。它是可重复性的，并且是标准化的，允许对损伤参数进行操作。LFP重述了在人类中观察到的损伤，从而使其具有临床相关性，并允许探索用于临床翻译的新疗法(20)。我们描述了在小鼠身上执行LFP程序的详细方案。造成的损伤是轻微到中度的，大脑皮质、海马体和胼胝体等区域最容易受到伤害。在LFP之后，将探索海马区和运动学习任务。
Traumatic brain injury (TBI) research has attained renewed momentum due to the increasing awareness of head injuries, which result in morbidity and mortality. Based on the nature of primary injury following TBI, complex and heterogeneous secondary consequences result, which are followed by regenerative processes (1,2). Primary injury can be induced by a direct contusion to the brain from skull fracture or from shearing and stretching of tissue causing displacement of brain due to movement (3,4). The resulting hematomas and lacerations cause a vascular response (3,5), and the morphological and functional damage of the white matter leads to diffuse axonal injury (6-8). Additional secondary changes commonly seen in the brain are edema and increased intracranial pressure (9). Following TBI there are microscopic alterations in biochemical and physiological pathways involving the release of excitotoxic neurotransmitters, immune mediators and oxygen radicals (10-12), which ultimately result in long-term neurological disabilities (13,14). Thus choosing appropriate animal models of TBI that present similar cellular and molecular events in human and rodent TBI is critical for studying the mechanisms underlying injury and repair.Various experimental models of TBI have been developed to reproduce aspects of TBI observed in humans, among them three specific models are widely adapted for rodents: fluid percussion, cortical impact and weight drop/impact acceleration (1). The fluid percussion device produces an injury through a craniectomy by applying a brief fluid pressure pulse on to the intact dura. The pulse is created by a pendulum striking the piston of a reservoir of fluid. The percussion produces brief displacement and deformation of neural tissue (1,15). Conversely, cortical impact injury delivers mechanical energy to the intact dura via a rigid impactor under pneumatic pressure (16,17). The weight drop/impact model is characterized by the fall of a rod with a specific mass on the closed skull (18). Among the TBI models, LFP is the most established and commonly used model to evaluate mixed focal and diffuse brain injury (19). It is reproducible and is standardized to allow for the manipulation of injury parameters. LFP recapitulates injuries observed in humans, thus rendering it clinically relevant, and allows for exploration of novel therapeutics for clinical translation (20).We describe the detailed protocol to perform LFP procedure in mice. The injury inflicted is mild to moderate, with brain regions such as cortex, hippocampus and corpus callosum being most vulnerable. Hippocampal and motor learning tasks are explored following LFP.