Grimmelt A-C, Eitzen S, Balakhadze I, Fischer B, Wölfer J, Schiffbauer H, Gorji A, Greiner C
University of Münster, Department of Neurosurgery, Germany.
Cent Eur Neurosurg. 2011 Aug;72(3):120-6. doi: 10.1055/s-0031-1271732. Epub 2011 Jul 7.
To date, there are only a few, non-evidence based, cerebroprotective therapeutic strategies for treatment and, accordingly, for prevention of secondary brain injuries following severe closed head trauma. In order to develop new therapy strategies, existing realistic animal models need to be advanced. The objective is to bridge standardized small animal models and actual patient medical care, since the results of experimental small animal studies often cannot be transferred to brain-injured humans. For improved standardization of high-velocity trauma, new trauma devices for initiating closed traumatic brain injury in sheep were developed. The following new devices were tested: 1. An anatomically shaped rubber bolt with an integrated oscillation absorber for prevention of skull fractures; 2. Stationary mounting of the bolt to guarantee stable experimental conditions; 3. Varying degrees of trauma severity, i. e., mild and severe closed traumatic brain injury, using different cartridges; and 4. Trauma analysis via high-speed video recording. Peritraumatic measurements of intracranial pressure, brain tissue pH, brain tissue oxygen, and carbon dioxide pressure, as well as neurotransmitter concentrations were performed. Cerebral injuries were documented with magnetic resonance imaging and compared to neuropathological results. Due to the new trauma devices, skull fractures were prevented. The high-speed video recording documented a realistic trauma mechanism for a car accident. Enhancement of extracellular glutamate, aspartate, and gamma amino butyric acid concentrations began 60 min after the trauma. Magnetic resonance imaging and neuropathological results showed characteristic injury patterns of mild, and severe, closed traumatic brain injury. The severe, closed traumatic brain injury group showed diffuse axonal injuries, traumatic subarachnoid hemorrhage, and hemorrhagic contusions with inconsistent distribution among the animals. The model presented here achieves a gain in standardization of severe, closed traumatic brain injury by increasing approximation to reality. The still existent heterogeneity of brain pathology mimics brain changes observed in patients after high-energy trauma. This model seems to close the gap between experimental small animal models and clinical studies. However, further investigations are needed to evaluate if this model can be used for testing new therapeutic strategies for these patients.
迄今为止，针对严重闭合性颅脑创伤后的治疗以及继发性脑损伤的预防，仅有少数几种缺乏循证依据的脑保护治疗策略。为了开发新的治疗策略，现有的实际动物模型需要改进。目标是在标准化的小动物模型和实际患者医疗护理之间建立桥梁，因为实验性小动物研究的结果往往无法应用于脑损伤患者。为提高高速创伤的标准化程度，开发了用于引发绵羊闭合性创伤性脑损伤的新型创伤装置。测试了以下新型装置：1. 带有集成减震器的解剖学形状橡胶螺栓，用于预防颅骨骨折；2. 螺栓的固定安装，以确保稳定的实验条件；3. 使用不同弹药筒实现不同程度的创伤严重性，即轻度和重度闭合性创伤性脑损伤；4. 通过高速视频记录进行创伤分析。进行了创伤周围颅内压、脑组织pH值、脑组织氧和二氧化碳压力以及神经递质浓度的测量。用磁共振成像记录脑损伤情况，并与神经病理学结果进行比较。由于采用了新型创伤装置，预防了颅骨骨折。高速视频记录记录了车祸的真实创伤机制。创伤后60分钟，细胞外谷氨酸、天冬氨酸和γ-氨基丁酸浓度开始升高。磁共振成像和神经病理学结果显示了轻度和重度闭合性创伤性脑损伤的特征性损伤模式。重度闭合性创伤性脑损伤组表现为弥漫性轴索损伤、创伤性蛛网膜下腔出血和出血性挫伤，在动物之间分布不一致。这里介绍的模型通过提高与现实的接近度，实现了重度闭合性创伤性脑损伤标准化程度的提升。脑病理学中仍然存在的异质性模拟了高能创伤后患者观察到的脑部变化。该模型似乎弥合了实验性小动物模型与临床研究之间的差距。然而，需要进一步研究来评估该模型是否可用于测试针对这些患者的新治疗策略。
