In vivo two-photon fluorescence microscopy reveals disturbed cerebral capillary blood flow and increased susceptibility to ischemic insults in diabetic mice

Ji Yun Huang, Li Tao Li, Huan Wang, Shuang Shuang Liu, Ying Mei Lu, Mei Hua Liao, Rong Rong Tao, Ling Juan Hong, Kohji Fukunaga, Zhong Chen, Christopher S. Wilcox, En Yin Lai, Feng Han

Research output: Contribution to journalArticlepeer-review

23 Citations (Scopus)

Abstract

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 CaMKII 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.

Original languageEnglish
Pages (from-to)816-822
Number of pages7
JournalCNS Neuroscience and Therapeutics
Volume20
Issue number9
DOIs
Publication statusPublished - 2014 Sep

Keywords

  • Capillary
  • Cerebral blood flow
  • Diabetes
  • Hyperglycemia
  • Ischemia
  • Two-photon laser-scanning microscopy

ASJC Scopus subject areas

  • Pharmacology
  • Psychiatry and Mental health
  • Physiology (medical)
  • Pharmacology (medical)

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