Graduate Entry Medical School and Materials and Surface Science Institute, University of Limerick, Limerick, Ireland.
Pharmacol Ther. 2011 May;130(2):106-13. doi: 10.1016/j.pharmthera.2011.01.001. Epub 2011 Jan 21.
Animal models are necessary to elucidate changes occurring after brain injury and to establish new therapeutic strategies towards a stage where drug efficacy in brain injured patients (against all classes of symptoms) can be predicted. In this review, six established animal models of head trauma, namely fluid percussion, rigid indentation, inertial acceleration, impact acceleration, weight-drop and dynamic cortical deformation are evaluated. While no single animal model is entirely successful in reproducing the complete spectrum of pathological changes observed after injury, the validity of these animal models including face, construct, etiological and construct validity and how the models constitute theories about brain injury is addressed. The various types of injury including contact (direct impact) and non-contact (acceleration/deceleration) and their associated pathologies are described. The neuropathologic classifications of brain injury including primary and secondary, focal and diffuse are discussed. Animal models and their compatibility with microdialysis studies are summarised particularly regarding the role of excitatory and inhibitory amino acid neurotransmitters. This review concludes that the study of neurotransmitter interactions within and between brain regions can facilitate the development of novel compounds targeted to treat those cognitive deficits not limited to a single pharmacological class and may be useful in the investigation of new therapeutic strategies and pharmacological testing for improved treatment for traumatic head injury.
动物模型对于阐明脑损伤后发生的变化以及建立新的治疗策略是必要的，以便在药物对脑损伤患者（针对所有症状类型）的疗效可以被预测的阶段进行研究。在这篇综述中，评估了六种已建立的头部创伤动物模型，即液压冲击、刚性压迫、惯性加速、冲击加速、落体和动态皮质变形。虽然没有单一的动物模型能够完全成功地复制损伤后观察到的所有病理变化，但这些动物模型的有效性，包括表面效度、结构效度、病因学效度和构建效度，以及这些模型如何构成关于脑损伤的理论，都得到了阐述。描述了各种类型的损伤，包括接触性（直接冲击）和非接触性（加速/减速）以及它们相关的病理学。讨论了脑损伤的神经病理学分类，包括原发性和继发性、局灶性和弥漫性。特别综述了动物模型及其与微透析研究的兼容性，特别是关于兴奋性和抑制性氨基酸神经递质的作用。本综述得出的结论是，研究脑内和脑间神经递质的相互作用可以促进针对治疗那些认知缺陷的新型化合物的开发，这些认知缺陷不仅限于单一的药理类别，并且可能有助于研究新的治疗策略和药理学测试，以改善创伤性脑损伤的治疗效果。
