Progression of vasogenic edema induced by activated microglia under permanent middle cerebral artery occlusion

Journal Article · Thu Feb 15 04:00:00 EST 2018 · Biochemical and Biophysical Research Communications

DOI:https://doi.org/10.1016/J.BBRC.2018.01.094· OSTI ID:23127403

Tanaka, Miki ^[1]; Ishihara, Yasuhiro ^[1]; Mizuno, Shodo ^[2]; Ishida, Atsuhiko ^[1]; Vogel, Christoph F. ^[3]; Tsuji, Mayumi ^[4]; Yamazaki, Takeshi ^[1]; Itoh, Kouichi ^[2]

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1. Laboratory of Molecular Brain Science, Graduate School of Integrated Arts and Sciences, Hiroshima University, Hiroshima, 739-8521 (Japan)
2. Laboratory for Pharmacotherapy and Experimental Neurology, Kagawa School of Pharmaceutical Sciences, Tokushima Bunri University, Kagawa, 769-2193 (Japan)
3. Center for Health and the Environment, University of California, Davis, Davis, CA, 95616 (United States)
4. Department of Environmental Health, University of Occupational and Environmental Health, Fukuoka, 807-8555 (Japan)

Highlights: • Vasogenic edema was visualized by superimposing TTC staining on T2WI. • Vasogenic edema moved from the ischemic core to the peripheral region. • Microglial activation was spread from the ischemic core to the peripheral region. • Microglial inhibition suppressed the progression of vasogenic edema. • Microglia are involved in vasogenic edema progression in ischemic stroke. Brain edema is a severe complication that accompanies ischemic stroke. Increasing evidence shows that inflammatory cytokines impair tight junctions of the blood-brain barrier, suggesting the involvement of microglia in brain edema. In this study, we examined the role of microglia in the progression of ischemic brain edema using mice with permanent middle cerebral artery occlusion. The intensity of T2-weighted imaging (T2WI) in the cerebral cortex and the striatum was elevated 3 h after occlusion and spread to peripheral regions of the ischemic hemisphere. Merged images of 2,3,5-triphenyl tetrazolium chloride staining and T2WI revealed the exact vasogenic edema region, which spread from the ischemic core to outside the ischemic region. Microglia were strongly activated in the ischemic region 3 h after occlusion and, notably, activated microglia were observed in the non-ischemic region 24 h after occlusion. Pretreatment with minocycline, an inhibitor of microglial activation clearly suppressed not only vasogenic edema but also infarct formation. We demonstrated in this study that vasogenic edema spreads from the ischemic core to the peripheral region, which can be elicited, at least in part, by microglial activation induced by ischemia.

• OSTI ID: 23127403
• Journal Information: Biochemical and Biophysical Research Communications, Journal Name: Biochemical and Biophysical Research Communications Journal Issue: 2 Vol. 496; ISSN 0006-291X; ISSN BBRCA9
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
CEREBRAL ARTERIES
CEREBRAL CORTEX
INFLAMMATION
ISCHEMIA
LYMPHOKINES
MICE
TETRAZOLIUM