Zilkha Neurogenetic Institute, University of Southern California, Los Angeles, CA, United States.
Department of Neurosurgery, Washington University School of Medicine, St. Louis, MO, United States.
Front Immunol. 2021 Nov 16;12:785519. doi: 10.3389/fimmu.2021.785519. eCollection 2021.
Cerebrovascular pathologies are commonly associated with dementia. Because air pollution increases arterial disease in humans and rodent models, we hypothesized that air pollution would also contribute to brain vascular dysfunction. We examined the effects of exposing mice to nanoparticulate matter (nPM; aerodynamic diameter ≤200 nm) from urban traffic and interactions with cerebral hypoperfusion. C57BL/6 mice were exposed to filtered air or nPM with and without bilateral carotid artery stenosis (BCAS) and analyzed by multiparametric MRI and histochemistry. Exposure to nPM alone did not alter regional cerebral blood flow (CBF) or blood brain barrier (BBB) integrity. However, nPM worsened the white matter hypoperfusion (decreased CBF on DSC-MRI) and exacerbated the BBB permeability (extravascular IgG deposits) resulting from BCAS. White matter MRI diffusion metrics were abnormal in mice subjected to cerebral hypoperfusion and worsened by combined nPM+BCAS. Axonal density was reduced equally in the BCAS cohorts regardless of nPM status, whereas nPM exposure caused demyelination in the white matter with or without cerebral hypoperfusion. In summary, air pollution nPM exacerbates cerebrovascular pathology and demyelination in the setting of cerebral hypoperfusion, suggesting that air pollution exposure can augment underlying cerebrovascular contributions to cognitive loss and dementia in susceptible elderly populations.
脑血管疾病通常与痴呆有关。由于空气污染会增加人类和啮齿动物模型的动脉疾病，我们假设空气污染也会导致脑血管功能障碍。我们研究了暴露于城市交通产生的纳米颗粒物质（nPM；空气动力学直径≤200nm）以及与大脑低灌注的相互作用对小鼠的影响。将 C57BL/6 小鼠暴露于过滤空气或 nPM 中，同时进行双侧颈动脉狭窄（BCAS），并通过多参数 MRI 和组织化学进行分析。单独暴露于 nPM 不会改变局部脑血流（CBF）或血脑屏障（BBB）的完整性。然而，nPM 会加重白质低灌注（DSC-MRI 上的 CBF 降低）并加剧由 BCAS 引起的 BBB 通透性（血管外 IgG 沉积）。在发生大脑低灌注的小鼠中，白质 MRI 扩散指标异常，并因 nPM+BCAS 的联合作用而恶化。无论 nPM 状态如何，BCAS 队列中的轴突密度都同样降低，而 nPM 暴露会导致白质脱髓鞘，无论是否存在大脑低灌注。总之，空气污染 nPM 会加剧大脑低灌注时的脑血管病理和脱髓鞘，这表明空气污染暴露可能会加剧易患老年人认知能力下降和痴呆症的潜在脑血管疾病。
