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In vivo optical activation of astrocytes as a potential therapeutic strategy for neurodegenerative diseases

机译:星形胶质细胞的体内光学激活作为神经退行性疾病的潜在治疗策略

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Neurovascular dysfunction in many neurodegenerative diseases, such as Alzheimer's disease (AD), reduces blood flow to affected brain areas and causes neuronal dysfunction and loss. A new optical imaging technique is developed to activate astrocytes in live animal models in order to investigate the increase of local cerebral blood flow as a potential therapeutic strategy for AD. The technique uses fluorescent labeling of vasculature and astrocytes coupled with intravital 2-photon microscopy to visualize the astrocyte-vasculature interactions in live animals. Using femtosecond laser stimulation, calcium uncaging is applied to specifically target and activate astrocytes in vivo with high spatial and temporal resolutions. Intravital 2-photon microscopy imaging was employed to demonstrate that single endfoot optical activation around an arteriole induced a 25% increase in arteriole diameter, which in turn increased cerebral local blood flow in down-stream capillaries. This quantitative result indicates the potential of using optical activation of astrocytes in afflicted brain areas of neurodegeneration to restore normal neurovascular functions.
机译:在许多神经退行性疾病(例如阿尔茨海默氏病(AD))中,神经血管功能障碍会减少流向受影响的大脑区域的血流量,并导致神经元功能障碍和丧失。为了研究局部脑血流量的增加作为AD的潜在治疗策略,开发了一种新的光学成像技术来激活活体动物模型中的星形胶质细胞。该技术使用脉管系统和星形胶质细胞的荧光标记结合活体2光子显微镜观察活体动物中的星形胶质细胞-脉管系统相互作用。使用飞秒激光刺激,将钙解笼应用于体内以高空间和时间分辨率特异性靶向并激活星形胶质细胞。使用玻璃体2光子显微镜成像来证明小动脉周围的单个尾足光学激活引起小动脉直径增加25%,从而增加下游毛细血管中的大脑局部血流量。该定量结果表明在患神经变性的脑部区域中使用星形胶质细胞的光活化来恢复正常神经血管功能的潜力。

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