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Treatment with Isorhamnetin Protects the Brain Against Ischemic Injury in Mice

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Abstract

Ischemic stroke is a major cause of morbidity and mortality, yet lacks effective neuroprotective treatments. The aim of this work was to investigate whether treatment with isorhamnetin protected the brain against ischemic injury in mice. Experimental stroke mice underwent the filament model of middle cerebral artery occlusion with reperfusion. Treatment with isorhamnetin or vehicle was initiated immediately at the onset of reperfusion. It was found that treatment of experimental stroke mice with isorhamnetin reduced infarct volume and caspase-3 activity (a biomarker of apoptosis), and improved neurological function recovery. Treatment of experimental stroke mice with isorhamnetin attenuated cerebral edema, improved blood–brain barrier function, and upregulated gene expression of tight junction proteins including occludin, ZO-1, and claudin-5. Treatment of experimental stroke mice with isorhamnetin activated Nrf2/HO-1, suppressed iNOS/NO, and led to reduced formation of MDA and 3-NT in ipsilateral cortex. In addition, treatment of experimental stroke mice with isorhamnetin suppressed activity of MPO (a biomarker of neutrophil infiltration) and reduced protein levels of IL-1β, IL-6, and TNF-α in ipsilateral cortex. Furthermore, it was found that treatment of experimental stroke mice with isorhamnetin reduced mRNA and protein expression of NMDA receptor subunit NR1 in ipsilateral cortex. In conclusion, treatment with isorhamnetin protected the brain against ischemic injury in mice. Isorhamnetin could thus be envisaged as a countermeasure for ischemic stroke but remains to be tested in humans.

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    Authors and Affiliations

    1. Department of Neurology, 305th Hospital of the People’s Liberation Army, Jia13 Wenjin Road, Beijing, 100017, China

      Jin-Jing Zhao & Kai Wang

    2. Department of Pediatrics, Peking University First Hospital, Beijing, 100034, China

      Jin-Qing Song

    3. Department of Hyperbaric Oxygen, Navy General Hospital of People’s Liberation Army, Beijing, 100048, China

      Shu-Yi Pan

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    1. Jin-Jing Zhao
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    4. Kai Wang
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    Correspondence to Kai Wang.

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    Jin-Jing Zhao and Jin-Qing Song have contributed equally to this work.

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    Zhao, JJ., Song, JQ., Pan, SY. et al. Treatment with Isorhamnetin Protects the Brain Against Ischemic Injury in Mice. Neurochem Res 41, 1939–1948 (2016). https://doi.org/10.1007/s11064-016-1904-2

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    • DOI: https://doi.org/10.1007/s11064-016-1904-2

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