Department of Neurosurgery and Neurology, University of Rochester Medical Center, Center for Neurodegenerative and Vascular Brain Disorders, Rochester, NY 14642, USA.
Neuron. 2010 Nov 4;68(3):409-27. doi: 10.1016/j.neuron.2010.09.043.
Pericytes play a key role in the development of cerebral microcirculation. The exact role of pericytes in the neurovascular unit in the adult brain and during brain aging remains, however, elusive. Using adult viable pericyte-deficient mice, we show that pericyte loss leads to brain vascular damage by two parallel pathways: (1) reduction in brain microcirculation causing diminished brain capillary perfusion, cerebral blood flow, and cerebral blood flow responses to brain activation that ultimately mediates chronic perfusion stress and hypoxia, and (2) blood-brain barrier breakdown associated with brain accumulation of serum proteins and several vasculotoxic and/or neurotoxic macromolecules ultimately leading to secondary neuronal degenerative changes. We show that age-dependent vascular damage in pericyte-deficient mice precedes neuronal degenerative changes, learning and memory impairment, and the neuroinflammatory response. Thus, pericytes control key neurovascular functions that are necessary for proper neuronal structure and function, and pericyte loss results in a progressive age-dependent vascular-mediated neurodegeneration.
周细胞在大脑微循环的发育中起着关键作用。然而，周细胞在成年大脑和大脑衰老过程中的神经血管单元中的确切作用仍然难以捉摸。利用成年存活的周细胞缺陷小鼠，我们发现周细胞缺失通过两条平行途径导致脑血管损伤：（1）脑微循环减少导致脑毛细血管灌注、脑血流和脑血流对大脑激活的反应减少，最终介导慢性灌注应激和缺氧；（2）血脑屏障破坏与脑内血清蛋白和几种血管毒性和/或神经毒性大分子的积累有关，最终导致继发性神经元退行性变化。我们发现，周细胞缺陷小鼠的年龄相关性血管损伤先于神经元退行性变化、学习和记忆障碍以及神经炎症反应。因此，周细胞控制着关键的神经血管功能，这些功能对于神经元的正常结构和功能是必需的，而周细胞缺失会导致进行性的、与年龄相关的血管介导的神经退行性变。
