Center for Translational Research in Neurodegenerative Disease (CTRND), University of Florida, Gainesville, FL 32610, USA; Department of Neuroscience, University of Florida, Gainesville, FL 32610, USA; McKnight Brain Institute, University of Florida, Gainesville, FL 32610, USA.
Department of Neuroscience, University of Florida, Gainesville, FL 32610, USA; Department of Computer of Information Science and Engineering (CISE), University of Florida, Gainesville, FL 32610, USA.
Neuroimage. 2024 Sep;298:120764. doi: 10.1016/j.neuroimage.2024.120764. Epub 2024 Jul 30.
Traumatic brain injuries (TBI) present a major public health challenge, demanding an in-depth understanding of age-specific symptoms and risk factors. Aging not only significantly influences brain function and plasticity but also elevates the risk of hospitalizations and death following TBIs. Repetitive mild TBIs (rmTBI) compound these issues, resulting in cumulative and long-term brain damage in the brain. In this study, we investigate the impact of age on brain network changes and white matter properties following rmTBI by employing a multi-modal approach that integrates resting-state functional magnetic resonance imaging (rsfMRI), graph theory analysis, diffusion tensor imaging (DTI), and neurite orientation dispersion and density imaging (NODDI). Our hypothesis is that the effects of rmTBI are worsened in aged animals, with this group showing more pronounced alterations in brain connectivity and white matter structure. Utilizing the closed-head impact model of engineered rotational acceleration (CHIMERA) model, we conducted rmTBIs or sham (control) procedures on young (2.5-3-months-old) and aged (22-months-old) male and female mice to model high-risk groups. Functional and structural imaging unveiled age-related reductions in communication efficiency between brain regions, while injuries induced opposhigh-risking effects on the small-world index across age groups, influencing network segregation. Functional connectivity analysis also identified alterations in 79 out of 148 brain regions by age, treatment (sham vs. rmTBI), or their interaction. Injuries exerted pronounced effects on sensory integration areas, including insular and motor cortices. Age-related disruptions in white matter integrity were observed, indicating alterations in various diffusion directions (mean diffusivity, radial diffusivity, axial diffusivity, and fractional anisotropy) and density neurite properties (dispersion index, intracellular and isotropic volume fraction). Neuroinflammation, assessed through Iba-1 and GFAP markers, correlated with higher dispersion in the optic tract, suggesting a neuroinflammatory response in injured aged animals compared to sham aged. These findings offer insight into the interplay between age, injuries, and brain connectivity, shedding light on the long-term consequences of rmTBI.
创伤性脑损伤 (TBI) 是一个主要的公共卫生挑战，需要深入了解特定年龄的症状和风险因素。年龄不仅会显著影响大脑功能和可塑性，还会增加 TBI 后住院和死亡的风险。重复性轻度 TBI (rmTBI) 使这些问题更加复杂，导致大脑中累积和长期的脑损伤。在这项研究中，我们通过使用多模态方法，包括静息态功能磁共振成像 (rsfMRI)、图论分析、扩散张量成像 (DTI) 和神经丝取向分散和密度成像 (NODDI)，研究年龄对 rmTBI 后大脑网络变化和白质特性的影响。我们的假设是，rmTBI 的影响在老年动物中更为严重，该组显示出更明显的大脑连接和白质结构改变。我们利用工程旋转加速度闭合头冲击模型 (CHIMERA) 模型，对年轻 (2.5-3 个月大) 和老年 (22 个月大) 雄性和雌性小鼠进行 rmTBI 或假手术 (对照) 处理，以模拟高风险组。功能和结构成像揭示了年龄相关的大脑区域之间通信效率的降低，而损伤对各年龄组的小世界指数产生了相反的影响，影响了网络分离。功能连接分析还确定了 148 个大脑区域中的 79 个区域因年龄、治疗 (假手术与 rmTBI) 或它们的相互作用而发生变化。损伤对感觉整合区域产生了显著影响，包括岛叶和运动皮层。观察到与年龄相关的白质完整性中断，表明各向异性扩散方向 (平均扩散率、径向扩散率、轴向扩散率和各向异性分数) 和神经丝密度特性 (分散指数、细胞内和各向同性体积分数) 发生改变。通过 Iba-1 和 GFAP 标志物评估的神经炎症与光神经束的更高分散性相关，这表明与假手术老年动物相比，受伤老年动物存在神经炎症反应。这些发现深入了解了年龄、损伤和大脑连接之间的相互作用，为 rmTBI 的长期后果提供了深入了解。
