Behavioral and Neural Activity-Dependent Recanalization of Plugged Capillaries in the Brain of Adult and Aged Mice.
Behavioral and Neural Activity-Dependent Recanalization of Plugged Capillaries in the Brain of Adult and Aged Mice.
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DOI：
10.3389/fncel.2022.876746
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发表时间：
2022
影响因子：
5.3
通讯作者：
Brown, Craig E.
中科院分区：
文献类型：
--
作者：
Reeson, Patrick;Schager, Ben;Van Sprengel, Myrthe;Brown, Craig E.
关键词：
大脑的毛细血管，由于其直径小和灌流压低，容易受到血流中断的影响。这些微小的闭塞可能会对血管结构和大脑功能产生过大的影响；特别是当疾病状态恶化或随着年龄的增长而积累时。大脑微血管系统的一个显著特征是活跃的神经元能够招募局部血流。神经活动与血流的偶联可能在阻塞的毛细血管再通中发挥重要作用。为了研究这一想法，我们通过注射荧光微球在小鼠身上实验诱导毛细血管阻塞，然后通过行为或药物方法操纵神经活动水平。我们发现，让成年和老年小鼠暴露在丰富的环境(集体住房、新奇的物体、运动轮)中12小时，足以显著降低整个前脑的阻塞毛细血管密度。为了更直接地操纵神经活动，我们在药物上抑制或增加了躯体感觉皮质中的神经元活动。当我们抑制皮质活动时，由于阻塞的毛细血管密度显著增加，再通受到损害。相反，皮质活动的增加改善了毛细血管的再通。由于全身心血管因素(心率、血压的变化)可以解释这些对血管再通的影响，我们证明，通过修剪胡须或注射蝇草酚的单侧神经活动操作，仍然对再通有显著的和半球特有的影响，即使在暴露于浓缩的小鼠中也是如此，那里的心血管影响在两个半球都是明显的。综上所述，我们的研究显示神经活动双向调节阻塞的毛细血管的再通。此外，我们还表明，通过行为参与(即，丰富环境)来刺激大脑活动可以在整个生命周期内促进血管健康。
The capillaries of the brain, owing to their small diameter and low perfusion pressure, are vulnerable to interruptions in blood flow. These tiny occlusions can have outsized consequences on angioarchitecture and brain function; especially when exacerbated by disease states or accumulate with aging. A distinctive feature of the brain’s microvasculature is the ability for active neurons to recruit local blood flow. The coupling of neural activity to blood flow could play an important role in recanalizing obstructed capillaries. To investigate this idea, we experimentally induced capillary obstructions in mice by injecting fluorescent microspheres and then manipulated neural activity levels though behavioral or pharmacologic approaches. We show that engaging adult and aged mice with 12 h exposure to an enriched environment (group housing, novel objects, exercise wheels) was sufficient to significantly reduce the density of obstructed capillaries throughout the forebrain. In order to more directly manipulate neural activity, we pharmacologically suppressed or increased neuronal activity in the somatosensory cortex. When we suppressed cortical activity, recanalization was impaired given the density of obstructed capillaries was significantly increased. Conversely, increasing cortical activity improved capillary recanalization. Since systemic cardiovascular factors (changes in heart rate, blood pressure) could explain these effects on recanalization, we demonstrate that unilateral manipulations of neural activity through whisker trimming or injection of muscimol, still had significant and hemisphere specific effects on recanalization, even in mice exposed to enrichment where cardiovascular effects would be evident in both hemispheres. In summary, our studies reveal that neural activity bi-directionally regulates the recanalization of obstructed capillaries. Further, we show that stimulating brain activity through behavioral engagement (i.e., environmental enrichment) can promote vascular health throughout the lifespan.
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影响因子：
7.7
作者：
Echagarruga CT;Gheres KW;Norwood JN;Drew PJ
通讯作者：
Drew PJ
影响因子：
8.8
作者：
El Amki, Mohamad;Glueck, Chaim;Wegener, Susanne
通讯作者：
Wegener, Susanne
影响因子：
6.3
作者：
Bekar, Lane K.;Wei, Helen S.;Nedergaard, Maiken
通讯作者：
Nedergaard, Maiken
DOI：
10.1093/brain/awab387
发表时间：
2022-05-24
期刊：
Brain : a journal of neurology
影响因子：
--
作者：
通讯作者：
--
DOI：
10.1073/pnas.1100428108
发表时间：
2011-05-17
影响因子：
11.1
作者：
Drew, Patrick J.;Shih, Andy Y.;Kleinfeld, David
通讯作者：
Kleinfeld, David