Kapapa Thomas, Wernheimer Vanida, Hoffmann Andrea, Merz Tamara, Zink Fabia, Wolfschmitt Eva-Maria, McCook Oscar, Vogt Josef, Wepler Martin, Messerer David Alexander Christian, Hartmann Claire, Scheuerle Angelika, Mathieu René, Mayer Simon, Gröger Michael, Denoix Nicole, Clazia Enrico, Radermacher Peter, Röhrer Stefan, Datzmann Thomas
Department of Neurosurgery, University Hospital Ulm, Albert-Einstein-Allee 23, 89081 Ulm, Germany.
Institute of Anaesthesiologic Pathophysiology and Process Development, University Hospital Ulm, Helmholtzstrasse 8/1, 89081 Ulm, Germany.
Cells. 2024 Dec 27;14(1):17. doi: 10.3390/cells14010017.
Traumatic brain injury (TBI) remains one of the leading causes of death. Because of the individual nature of the trauma (brain, circumstances and forces), humans experience individual TBIs. This makes it difficult to generalise therapies. Clinical management issues such as whether intracranial pressure (ICP), cerebral perfusion pressure (CPP) or decompressive craniectomy improve patient outcome remain partly unanswered. Experimental drug approaches for the treatment of secondary brain injury (SBI) have not found clinical application. The complex, cellular and molecular pathways of SBI remain incompletely understood, and there are insufficient experimental (animal) models that reflect the pathophysiology of human TBI to develop translational therapeutic approaches. Therefore, we investigated different injury patterns after acute subdural hematoma (ASDH) as TBI in a post-hoc approach to assess the impact on SBI in a long-term, human-sized porcine TBI animal model. Post-mortem brain tissue analysis, after ASDH, bilateral ICP, CPP, cerebral oxygenation and temperature monitoring, and biomarker analysis were performed. Extracerebral, intraparenchymal-extraventricular and intraventricular blood, combined with brainstem and basal ganglia injury, influenced the experiment and its outcome. Basal ganglia injury affects the duration of the experiment. Recognition of these different injury patterns is important for translational interpretation of results in this animal model of SBI after TBI.
创伤性脑损伤（TBI）仍然是主要死因之一。由于创伤的个体性（脑部、环境和外力），人类经历的TBI各不相同。这使得治疗方法难以一概而论。诸如颅内压（ICP）、脑灌注压（CPP）或减压颅骨切除术是否能改善患者预后等临床管理问题仍部分未得到解答。治疗继发性脑损伤（SBI）的实验性药物方法尚未在临床上得到应用。SBI复杂的细胞和分子途径仍未完全了解，而且缺乏足够反映人类TBI病理生理学的实验（动物）模型来开发转化性治疗方法。因此，我们采用事后分析方法，在一个长期的、与人类大小相当的猪TBI动物模型中，研究急性硬膜下血肿（ASDH）作为TBI后的不同损伤模式，以评估其对SBI的影响。在ASDH后进行了尸检脑组织分析、双侧ICP、CPP、脑氧合和温度监测以及生物标志物分析。脑外、脑实质内-脑室外和脑室内出血，以及脑干和基底节损伤，影响了实验及其结果。基底节损伤影响实验持续时间。识别这些不同的损伤模式对于在这个TBI后SBI动物模型中对结果进行转化性解释很重要。
