Soni Neha, Medeiros Rodrigo, Alateeq Khawlah, To Xuan Vinh, Nasrallah Fatima A
Queensland Brain Institute, The University of Queensland, St. Lucia, QLD, Australia.
Front Neurosci. 2021 Feb 24;15:611451. doi: 10.3389/fnins.2021.611451. eCollection 2021.
Traumatic brain injury (TBI) has been linked with tauopathy. However, imaging methods that can non-invasively detect tau-protein abnormalities following TBI need further investigation. This study aimed to investigate the potential of diffusion tensor imaging (DTI) to detect tauopathy following TBI in P301L mutant-tau-transgenic-pR5-mice. A total of 24 9-month-old pR5 mice were randomly assigned to sham and TBI groups. Controlled cortical injuries/craniotomies were performed for TBI/sham groups followed by DTI data acquisition on days 1 and 7 post-injury. DTI data were analyzed by using voxelwise analysis and track-based spatial statistics for gray matter and white matter. Further, immunohistochemistry was performed for total-tau and phosphorylated-tau, astrocytes, and microglia. To detect the association of DTI with these pathological markers, a correlation analysis was performed between DTI and histology findings. At day 1 post-TBI, DTI revealed a widespread reduction in fractional anisotropy (FA) and axial diffusivity (AxD) in the TBI group compared to shams. On day 7, further reduction in FA, AxD, and mean diffusivity and increased radial diffusivity were observed. FA was significantly increased in the amygdala and cortex. Correlation results showed that in the ipsilateral hemisphere FA reduction was associated with increased phosphorylated-tau and glial-immunoreactivity, whereas in the contralateral regions, the FA increase was associated with increased immunostaining for astrocytes. This study is the first to exploit DTI to investigate the effect of TBI in tau-transgenic mice. We show that alterations in the DTI signal were associated with glial activity following TBI and would most likely reflect changes that co-occur with/without phosphorylated-tau. In addition, FA may be a promising measure to identify discrete pathological processes such as increased astroglia activation, tau-hyperphosphorylation or both in the brain following TBI.
创伤性脑损伤（TBI）与tau蛋白病有关。然而，能够在创伤性脑损伤后非侵入性检测tau蛋白异常的成像方法仍需进一步研究。本研究旨在探讨弥散张量成像（DTI）在检测P301L突变型tau转基因-pR5小鼠创伤性脑损伤后tau蛋白病方面的潜力。总共24只9个月大的pR5小鼠被随机分为假手术组和创伤性脑损伤组。对创伤性脑损伤组/假手术组进行控制性皮质损伤/开颅手术，然后在损伤后第1天和第7天采集DTI数据。使用体素分析和基于轨迹的空间统计方法对灰质和白质的DTI数据进行分析。此外，对总tau蛋白和磷酸化tau蛋白、星形胶质细胞和小胶质细胞进行免疫组织化学检测。为了检测DTI与这些病理标志物的关联，对DTI和组织学结果进行了相关性分析。创伤性脑损伤后第1天，与假手术组相比，DTI显示创伤性脑损伤组的分数各向异性（FA）和轴向扩散率（AxD）普遍降低。在第7天，观察到FA、AxD和平均扩散率进一步降低，径向扩散率增加。杏仁核和皮质中的FA显著增加。相关性结果表明，在同侧半球，FA降低与磷酸化tau蛋白增加和胶质细胞免疫反应性增加有关，而在对侧区域，FA增加与星形胶质细胞免疫染色增加有关。本研究首次利用DTI研究创伤性脑损伤对tau转基因小鼠的影响。我们表明，DTI信号的改变与创伤性脑损伤后的胶质细胞活动有关，很可能反映了伴有或不伴有磷酸化tau蛋白的共同变化。此外，FA可能是识别创伤性脑损伤后大脑中离散病理过程（如星形胶质细胞激活增加、tau蛋白过度磷酸化或两者兼有）的一种有前景的指标。
