The Queensland Brain Institute, The University of Queensland, St. Lucia, QLD, Australia.
The Queensland Brain Institute, The University of Queensland, St. Lucia, QLD, Australia; The University of California, Irvine, United States.
Brain Res. 2022 Aug 15;1789:147955. doi: 10.1016/j.brainres.2022.147955. Epub 2022 May 27.
Traumatic Brain Injury (TBI) is often associated with long-term cognitive deficits and altered brain networks which have been linked with accumulation of neurofibrillary tau tangles and neuroinflammation. In this work, we investigated the changes in the brain post-TBI in an Alzheimer's disease pR5 tauopathy model and evaluated the contribution of tauopathy and neuroinflammation to connectivity alterations using resting-state functional Magnetic Resonance Imaging (rs-fMRI).
26 P301L tau transgenic mice of 8-9 months of age (21-35 g) expressing the human tau isoform carrying the pathogenic P301L mutation were used for the study. Animals were assessed at day 1 and 7 post-injury/craniotomy and were randomly divided into four groups. All animals underwent an MRI scan on a 9.4T Bruker system where rsfMRI was acquired. Following imaging, brains were stained with pSer (396 + 404), glial fibrillary acidic protein (GFAP), and ionised calcium-binding adaptor molecule-1 (Iba-1). Group-information-guided Independent Component Analysis (GIG-ICA) and region-of-interest (ROI)-based network connectivity approaches were applied. Principal Component Regression was applied to predict connectivity network strength from the corresponding ROIs.
TBI mice showed decreased functional connectivity in the dentate gyrus, thalamus, and other areas compared to sham animals at day 1 post-injury with the majority of changes resolving at day 7. Principal Component Regression showed only the contralateral CA1 network strength was correlated with the CA1's astrocyte and microglia cell density and the ipsilateral thalamus network strength was correlated with the ipsilateral thalamus' astrocyte and microglia cell density.
We present the first report on the temporal alterations in functional connectivity in a P30IL mouse model following TBI. Connectivity between key regions known to be affected in Alzheimer's disease were short-term and reversible following injury. Connectivity strength in CA1 and thalamus showed significant correlation with astrocyte and microglial cell density but not tau density.
创伤性脑损伤（TBI）常伴有长期认知缺陷和大脑网络改变，这些改变与神经原纤维缠结和神经炎症的积累有关。在这项工作中，我们研究了阿尔茨海默病 pR5tau 病模型中 TBI 后的大脑变化，并使用静息态功能磁共振成像（rs-fMRI）评估了 tau 病和神经炎症对连接改变的贡献。
我们使用了 26 只 8-9 个月大（21-35g）的 P301L tau 转基因小鼠，这些小鼠表达携带致病性 P301L 突变的人类 tau 同工型。动物在损伤/开颅后第 1 天和第 7 天进行评估，并随机分为四组。所有动物均在 Bruker 9.4T 系统上进行 MRI 扫描，采集 rsfMRI。成像后，用 pSer（396+404）、胶质纤维酸性蛋白（GFAP）和离子钙结合衔接蛋白-1（Iba-1）对大脑进行染色。采用基于群组信息的独立成分分析（GIG-ICA）和基于感兴趣区域（ROI）的网络连接方法。应用主成分回归来预测来自相应 ROI 的连接网络强度。
与假手术动物相比，TBI 小鼠在损伤后第 1 天，齿状回、丘脑和其他区域的功能连接减少，大多数变化在第 7 天得到解决。主成分回归显示，只有对侧 CA1 网络强度与 CA1 星形胶质细胞和小胶质细胞密度相关，同侧丘脑网络强度与同侧丘脑星形胶质细胞和小胶质细胞密度相关。
我们首次报道了 P30IL 小鼠模型 TBI 后功能连接的时间变化。已知在阿尔茨海默病中受影响的关键区域之间的连接是短暂的，并且在损伤后是可逆的。CA1 和丘脑的连接强度与星形胶质细胞和小胶质细胞密度显著相关，但与 tau 密度无关。
