University of British Columbia, Vancouver, BC, Canada.
Department of Pathology and Laboratory Medicine, Djavad Mowafaghian Centre for Brain Health, International Collaboration on Repair Discoveries, School of Biomedical Engineering, University of British Columbia, Vancouver, BC, Canada.
Adv Neurobiol. 2024;42:263-283. doi: 10.1007/978-3-031-69832-3_13.
Traumatic brain injury (TBI) is a leading cause of injury-related death and disability. In high-income countries, TBI is most prevalent among the older population (≥65 years), commonly caused by falls. Though age at injury is associated with increased risk of mortality and poor outcome, the underlying mechanisms are unclear. Studies in animal models may yield insights into the intersection of TBI with age. Here we review recent studies in animal models where TBI induced in aged animals is associated with exacerbated behavioral deficits (e.g., mortality, thigmotaxis, and cognitive deficits), neuropathology (microgliosis and astrogliosis), neuroinflammation (e.g., cytokines and iNOS), microglial alterations (e.g., more cellular vesicles and adopting a damage-associated microglia gene signature), and cell signaling and pathway changes (e.g., complement, phagocytosis, autophagy, trophic factor signaling). As relatively few preclinical studies focus on aged animals, more research is needed to fully understand the pathophysiology of TBI in the aged population. Particularly, we recommend that (1) more aged animals should be used, (2) closed-head TBI models should be considered, and (3) animal models of comorbidity or polytrauma should be considered.
创伤性脑损伤（TBI）是导致与损伤相关的死亡和残疾的主要原因。在高收入国家，TBI 最常见于老年人群体（≥65 岁），通常由跌倒引起。尽管受伤时的年龄与死亡率增加和预后不良有关，但潜在机制尚不清楚。动物模型中的研究可能会深入了解 TBI 与年龄的交叉点。在这里，我们回顾了最近在老年动物中诱导 TBI 的动物模型研究，这些研究与行为缺陷（例如死亡率、触壁反应和认知缺陷）、神经病理学（小胶质细胞增生和星形胶质细胞增生）、神经炎症（例如细胞因子和 iNOS）、小胶质细胞改变（例如更多的细胞囊泡和采用与损伤相关的小胶质细胞基因特征）以及细胞信号转导和途径变化（例如补体、吞噬作用、自噬、营养因子信号转导）有关。由于相对较少的临床前研究关注老年动物，因此需要更多的研究来充分了解老年人群体中 TBI 的病理生理学。特别是，我们建议：（1）应使用更多的老年动物，（2）应考虑闭合性颅脑损伤模型，以及（3）应考虑合并症或多发伤的动物模型。
