Open AccessIn Vivo Two‐photon Fluorescence Microscopy Reveals Disturbed Cerebral Capillary Blood Flow and Increased Susceptibility to Ischemic Insults in Diabetic Mice
Author(s) -
Huang JiYun,
Li LiTao,
Wang Huan,
Liu ShuangShuang,
Lu YingMei,
Liao MeiHua,
Tao RongRong,
Hong LingJuan,
Fukunaga Kohji,
Chen Zhong,
Wilcox Christopher S.,
Lai En Yin,
Han Feng
Publication year - 2014
Publication title -
cns neuroscience and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 69
eISSN - 1755-5949
pISSN - 1755-5930
DOI - 10.1111/cns.12268
Subject(s) - cerebral blood flow , medicine , ischemia , diabetes mellitus , microcirculation , blood flow , in vivo , cerebral circulation , pathology , endocrinology , biology , microbiology and biotechnology
Summary Aims Diabetes mellitus increases the risk of stroke, but the mechanisms are unclear. The present study tested the hypothesis that diabetes mellitus disturbs the brain microcirculation and increases the susceptibility to cerebral damage in a middle cerebral artery occlusion ( MCAO ) model of ischemia. Methods Diabetes was induced by streptozocin in mice expressing green fluorescent protein in endothelial cells (Tie2‐ GFP mice). Four weeks later, they were subjected to transient (20 min) MCAO . In vivo blood flow was measured by two‐photon laser‐scanning microscopy ( TPLSM ) in cerebral arteries, veins, and capillaries. Results There was a significant decrease in red blood cell ( RBC ) velocity in capillaries in diabetic mice as assessed by TPLSM , yet the regional cerebral blood flow, as assessed by laser Doppler flowmetry, was maintained. Brain capillary flow developed turbulence after MCAO only in diabetic mice. These mice sustained increased neurological deficits after MCAO which were accompanied by an exaggerated degradation of tight junction proteins and blunted Ca MKII phosphorylation in cerebral tissues indicating disruption of the blood–brain barrier and disturbed cognitive potential. Conclusion Diabetic mice are more susceptible to disturbances of cerebral capillary blood flow which may predispose them to neurovascular defects following ischemia.