Syeda Warda, Ermine Charlotte M, Khilf Mohamed Salah, Wright David, Brait Vanessa H, Nithianantharajah Jess, Kolbe Scott, Johnston Leigh A, Thompson Lachlan H, Brodtmann Amy
The Florey Institute of Neuroscience and Mental Health, Parkville, Victoria, Australia.
Department of Neuroscience, Monash University, Clayton, Australia.
Brain Commun. 2022 Jul 22;4(4):fcac185. doi: 10.1093/braincomms/fcac185. eCollection 2022.
Preclinical studies of remote degeneration have largely focused on brain changes over the first few days or weeks after stroke. Accumulating evidence suggests that neurodegeneration occurs in other brain regions remote to the site of infarction for months and even years following ischaemic stroke. Brain atrophy appears to be driven by both axonal degeneration and widespread brain inflammation. The evolution and duration of these changes are increasingly being described in human studies, using advanced brain imaging techniques. Here, we sought to investigate long-term structural brain changes in a model of mild focal ischaemic stroke following injection of endothlin-1 in adult Long-Evans rats ( = 14) compared with sham animals ( = 10), over a clinically relevant time-frame of 48 weeks. Serial structural and diffusion-weighted MRI data were used to assess dynamic volume and white matter trajectories. We observed dynamic regional brain volume changes over the 48 weeks, reflecting both normal changes with age in sham animals and neurodegeneration in regions connected to the infarct following ischaemia. Ipsilesional cortical volume loss peaked at 24 weeks but was less prominent at 36 and 48 weeks. We found significantly reduced fractional anisotropy in both ipsi- and contralesional motor cortex and cingulum bundle regions of infarcted rats ( < 0.05) from 4 to 36 weeks, suggesting ongoing white matter degeneration in tracts connected to but distant from the stroke. We conclude that there is evidence of significant cortical atrophy and white matter degeneration up to 48 weeks following infarct, consistent with enduring, pervasive stroke-related degeneration.
远程变性的临床前研究主要集中在中风后的头几天或几周内大脑的变化。越来越多的证据表明，在缺血性中风后的数月甚至数年里，神经变性发生在梗死部位以外的其他脑区。脑萎缩似乎是由轴突变性和广泛的脑部炎症共同驱动的。利用先进的脑成像技术，这些变化的演变和持续时间在人体研究中越来越多地得到描述。在这里，我们试图研究成年Long-Evans大鼠（n = 14）与假手术动物（n = 10）相比，在注射内皮素-1后轻度局灶性缺血性中风模型中，在48周的临床相关时间范围内的长期脑结构变化。连续的结构和扩散加权MRI数据用于评估动态体积和白质轨迹。我们观察到在48周内动态区域脑体积变化，这既反映了假手术动物随年龄的正常变化，也反映了缺血后与梗死灶相连区域的神经变性。患侧皮质体积损失在24周时达到峰值，但在36周和48周时不太明显。我们发现，梗死大鼠的患侧和对侧运动皮层以及扣带束区域的分数各向异性在4至36周时显著降低（P < 0.05），表明与中风相连但距离较远的脑区存在持续的白质变性。我们得出结论，有证据表明梗死48周后存在明显的皮质萎缩和白质变性，这与持久、广泛的中风相关变性一致。
