Tan Sheryl, Hamlin Danica, Kwon Eryn, Scadeng Miriam, Shim Vickie, Holdsworth Samantha, Guild Sarah-Jane, Murray Helen
Centre for Brain Research, University of Auckland, Grafton, New Zealand.
Department of Anatomy and Medical Imaging, University of Auckland, Grafton, New Zealand.
Neurotrauma Rep. 2024 Mar 6;5(1):194-202. doi: 10.1089/neur.2023.0105. eCollection 2024.
Large animal models of mild traumatic brain injury (mTBI) are needed to elucidate the pathophysiology of mechanical insult to a gyrencephalic brain. Sheep (ovis aries) are an attractive model for mTBI because of their neuroanatomical similarity to humans; however, few histological studies of sheep mTBI models have been conducted. We previously developed a sheep mTBI model to pilot methods for investigating the mechanical properties of brain tissue after injury. Here, we sought to histologically characterize the cortex under the impact site in this model. Three animals received a closed skull mTBI with unconstrained head motion, delivered with an impact stunner, and 3 sham animals were anesthetized but did not receive an impact. Magnetic resonance imaging (MRI) of the brain was performed before and after the impact and revealed variable degrees of damage to the skull and brain. Fluorescent immunohistochemistry revealed regions of hemorrhage in the cortex underlying the impact site in 2 of 3 mTBI sheep, the amount of which correlated with the degree of damage observed on the post-impact MRI scans. Labeling for microtubule-associated protein 2 and neuronal nuclear protein revealed changes in cellular anatomy, but, unexpectedly, glial fibrillary acidic protein and ionized calcium-binding adaptor molecule 1 labeling were relatively unchanged compared to sham animals. Our findings provide preliminary evidence of vascular and neuronal damage with limited glial reactivity and highlight the need for further in-depth histological assessment of large animal mTBI models.
需要大型轻度创伤性脑损伤(mTBI)动物模型来阐明对脑回脑机械性损伤的病理生理学。绵羊(ovis aries)因其神经解剖结构与人类相似,是mTBI的一种有吸引力的模型;然而,对绵羊mTBI模型的组织学研究很少。我们之前开发了一种绵羊mTBI模型,以试验研究损伤后脑组织力学特性的方法。在此,我们试图对该模型中撞击部位下方的皮质进行组织学特征描述。三只动物接受了使用撞击致晕器造成的头部无约束的闭合性颅骨mTBI,三只假手术动物进行了麻醉但未接受撞击。在撞击前后对大脑进行磁共振成像(MRI),结果显示颅骨和大脑有不同程度的损伤。荧光免疫组织化学显示,在三只mTBI绵羊中的两只,撞击部位下方的皮质有出血区域,其出血量与撞击后MRI扫描观察到的损伤程度相关。微管相关蛋白2和神经元核蛋白的标记显示细胞解剖结构有变化,但出乎意料的是,与假手术动物相比,胶质纤维酸性蛋白和离子钙结合衔接分子1的标记相对未发生变化。我们的研究结果提供了血管和神经元损伤且胶质反应有限的初步证据,并强调了对大型动物mTBI模型进行进一步深入组织学评估的必要性。