title: Vasodilation by in vivo activation of astrocyte endfeet via two-photon calcium uncaging as a strategy to prevent brain ischemia.
abstract: Decreased cerebral blood flow causes brain ischemia and plays an important role in the pathophysiology of many neurodegenerative diseases, including Alzheimer's disease and vascular dementia. In this study, we photomodulated astrocytes in the live animal by a combination of two-photon calcium uncaging in the astrocyte endfoot and in vivo imaging of neurovasculature and astrocytes by intravital two-photon microscopy after labeling with cell type specific fluorescent dyes. Our study demonstrates that photomodulation at the endfoot of a single astrocyte led to a 25% increase in the diameter of a neighboring arteriole, which is a crucial factor regulating cerebral microcirculation in downstream capillaries. Two-photon uncaging in the astrocyte soma or endfoot near veins does not show the same effect on microcirculation. These experimental results suggest that infrared photomodulation on astrocyte endfeet may be a strategy to increase cerebral local microcirculation and thus prevent brain ischemia.
authors.affiliation: Weill Cornell Medical College, Houston Methodist Research Institute, \Systems Medicine and Bioengineering Department, TT and WF Chao Center for BRAIN, Houston, Texas 77030.
authors.forename: Yuanxin
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Weill Cornell Medical College, Houston Methodist Research Institute, \Systems Medicine and Bioengineering Department, TT and WF Chao Center for BRAIN, Houston, Texas 77030.
authors.forename: James
authors.initials: J
authors.lastname: Mancuso
authors.affiliation: Weill Cornell Medical College, Houston Methodist Research Institute, \Systems Medicine and Bioengineering Department, TT and WF Chao Center for BRAIN, Houston, Texas 77030bSoutheast University, Zhongda Hospital, Medical School, Department of Radiology, Jiangsu Key Laboratory of Molecular and Functional Imaging, Nanjing 210009, China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Zhao
authors.affiliation: Weill Cornell Medical College, Houston Methodist Research Institute, \Systems Medicine and Bioengineering Department, TT and WF Chao Center for BRAIN, Houston, Texas 77030.
authors.forename: Xuping
authors.initials: X
authors.lastname: Li
authors.affiliation: Weill Cornell Medical College, Houston Methodist Research Institute, \Systems Medicine and Bioengineering Department, TT and WF Chao Center for BRAIN, Houston, Texas 77030.
authors.forename: Jie
authors.initials: J
authors.lastname: Cheng
authors.affiliation: Weill Cornell Medical College, Houston Methodist Hospital, Nantz National Alzheimer Center, Houston, Texas 77030.
authors.forename: Gustavo
authors.initials: G
authors.lastname: Roman
authors.affiliation: Weill Cornell Medical College, Houston Methodist Research Institute, \Systems Medicine and Bioengineering Department, TT and WF Chao Center for BRAIN, Houston, Texas 77030.
authors.forename: Stephen T C
authors.initials: ST
authors.lastname: Wong
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000528:radiation effects*; D002545:Brain Ischemia / Q000517:prevention & control*; D002118:Calcium / Q000378:metabolism*; D002560:Cerebrovascular Circulation / Q000528:radiation effects*; D007259:Infrared Rays; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008833:Microcirculation / Q000528:radiation effects; D036641:Microscopy, Fluorescence, Multiphoton; D014664:Vasodilation / Q000528:radiation effects*
chemical_list: D002118:Calcium