PMID- 25370583 OWN - NLM STAT- MEDLINE DCOM- 20150121 LR - 20220408 IS - 1524-4628 (Electronic) IS - 0039-2499 (Linking) VI - 45 IP - 12 DP - 2014 Dec TI - In vivo imaging of the mouse neurovascular unit under chronic cerebral hypoperfusion. PG - 3698-703 LID - 10.1161/STROKEAHA.114.005891 [doi] AB - BACKGROUND AND PURPOSE: Proper brain function is maintained by an integrated system called the neurovascular unit (NVU) comprised cellular and acellular elements. Although the individual features of specific neurovascular components are understood, it is unknown how they respond to ischemic stress as a functional unit. Therefore, we established an in vivo imaging method and clarified the NVU response to chronic cerebral hypoperfusion. METHODS: Green mice (b-act-EGFP) with SR101 plasma labeling were used in this experiment. A closed cranial window was made over the left somatosensory cortex. To mimic chronic cerebral hypoperfusion, mice were subjected to bilateral common carotid artery stenosis operations using microcoils. In vivo real-time imaging was performed using 2-photon laser-scanning microscopy during the preoperative period, and after 1 day and 1 and 2 weeks of bilateral common carotid artery stenosis or sham operations. RESULTS: Our method allowed 3-dimensional observation of most of the components of the NVU, as well as dynamic capillary microcirculation. Under chronic cerebral hypoperfusion, we did not detect any structural changes of each cellular component in the NVU; however, impairment of microcirculation was detected over a prolonged period. In the pial small arteries and veins, rolling and adhesion of leukocyte were detected, more prominently in the latter. In the deep cortical capillaries, flow stagnation because of leukocyte plugging was frequently observed. CONCLUSIONS: We established an in vivo imaging method for real-time visualization of the NVU. It seems that under chronic cerebral hypoperfusion, leukocyte activation has a critical role in microcirculation disturbance. CI - (c) 2014 American Heart Association, Inc. FAU - Yata, Kenichiro AU - Yata K AD - From the Department of Neurology (K.Y., H.T.), Department of Molecular and Cellular Pharmacology, Pharmacogenomics and Pharmacoinformatics (Y.N., T.T.), and Department of Neural Regeneration and Cell Communication (A.M.), Mie University Graduate School of Medicine, Tsu, Mie, Japan; and Department of Neurology, Keio University School of Medicine, Shinjuku, Tokyo, Japan (M.U., Y.T., N.S.). ken-yata@mbk.nifty.com. FAU - Nishimura, Yuhei AU - Nishimura Y AD - From the Department of Neurology (K.Y., H.T.), Department of Molecular and Cellular Pharmacology, Pharmacogenomics and Pharmacoinformatics (Y.N., T.T.), and Department of Neural Regeneration and Cell Communication (A.M.), Mie University Graduate School of Medicine, Tsu, Mie, Japan; and Department of Neurology, Keio University School of Medicine, Shinjuku, Tokyo, Japan (M.U., Y.T., N.S.). FAU - Unekawa, Miyuki AU - Unekawa M AD - From the Department of Neurology (K.Y., H.T.), Department of Molecular and Cellular Pharmacology, Pharmacogenomics and Pharmacoinformatics (Y.N., T.T.), and Department of Neural Regeneration and Cell Communication (A.M.), Mie University Graduate School of Medicine, Tsu, Mie, Japan; and Department of Neurology, Keio University School of Medicine, Shinjuku, Tokyo, Japan (M.U., Y.T., N.S.). FAU - Tomita, Yutaka AU - Tomita Y AD - From the Department of Neurology (K.Y., H.T.), Department of Molecular and Cellular Pharmacology, Pharmacogenomics and Pharmacoinformatics (Y.N., T.T.), and Department of Neural Regeneration and Cell Communication (A.M.), Mie University Graduate School of Medicine, Tsu, Mie, Japan; and Department of Neurology, Keio University School of Medicine, Shinjuku, Tokyo, Japan (M.U., Y.T., N.S.). FAU - Suzuki, Norihiro AU - Suzuki N AD - From the Department of Neurology (K.Y., H.T.), Department of Molecular and Cellular Pharmacology, Pharmacogenomics and Pharmacoinformatics (Y.N., T.T.), and Department of Neural Regeneration and Cell Communication (A.M.), Mie University Graduate School of Medicine, Tsu, Mie, Japan; and Department of Neurology, Keio University School of Medicine, Shinjuku, Tokyo, Japan (M.U., Y.T., N.S.). FAU - Tanaka, Toshio AU - Tanaka T AD - From the Department of Neurology (K.Y., H.T.), Department of Molecular and Cellular Pharmacology, Pharmacogenomics and Pharmacoinformatics (Y.N., T.T.), and Department of Neural Regeneration and Cell Communication (A.M.), Mie University Graduate School of Medicine, Tsu, Mie, Japan; and Department of Neurology, Keio University School of Medicine, Shinjuku, Tokyo, Japan (M.U., Y.T., N.S.). FAU - Mizoguchi, Akira AU - Mizoguchi A AD - From the Department of Neurology (K.Y., H.T.), Department of Molecular and Cellular Pharmacology, Pharmacogenomics and Pharmacoinformatics (Y.N., T.T.), and Department of Neural Regeneration and Cell Communication (A.M.), Mie University Graduate School of Medicine, Tsu, Mie, Japan; and Department of Neurology, Keio University School of Medicine, Shinjuku, Tokyo, Japan (M.U., Y.T., N.S.). FAU - Tomimoto, Hidekazu AU - Tomimoto H AD - From the Department of Neurology (K.Y., H.T.), Department of Molecular and Cellular Pharmacology, Pharmacogenomics and Pharmacoinformatics (Y.N., T.T.), and Department of Neural Regeneration and Cell Communication (A.M.), Mie University Graduate School of Medicine, Tsu, Mie, Japan; and Department of Neurology, Keio University School of Medicine, Shinjuku, Tokyo, Japan (M.U., Y.T., N.S.). LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20141104 PL - United States TA - Stroke JT - Stroke JID - 0235266 RN - 147336-22-9 (Green Fluorescent Proteins) SB - IM MH - Animals MH - Brain/*pathology MH - Brain Ischemia/*pathology MH - Green Fluorescent Proteins/genetics MH - Imaging, Three-Dimensional/methods MH - Male MH - Mice MH - Mice, Transgenic MH - Microscopy, Confocal/methods MH - Neuroimaging/*methods OTO - NOTNLM OT - astrocytes OT - leukocytes OT - microcirculation OT - microscopy, fluorescence, multiphoton OT - pericytes EDAT- 2014/11/06 06:00 MHDA- 2015/01/22 06:00 CRDT- 2014/11/06 06:00 PHST- 2014/11/06 06:00 [entrez] PHST- 2014/11/06 06:00 [pubmed] PHST- 2015/01/22 06:00 [medline] AID - STROKEAHA.114.005891 [pii] AID - 10.1161/STROKEAHA.114.005891 [doi] PST - ppublish SO - Stroke. 2014 Dec;45(12):3698-703. doi: 10.1161/STROKEAHA.114.005891. Epub 2014 Nov 4.