Irisin Peptide Protects Brain Against Ischemic Injury Through Reducing Apoptosis and Enhancing BDNF in a Rodent Model of Stroke

Asadi, Y. and Gorjipour, F. and Behrouzifar, S. and Vakili, A. (2018) Irisin Peptide Protects Brain Against Ischemic Injury Through Reducing Apoptosis and Enhancing BDNF in a Rodent Model of Stroke. Neurochemical Research, 43 (8). pp. 1549-1560.

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Evidence has shown therapeutic potential of irisin in cerebral stroke. The present study aimed to assess the effects of recombinant irisin on the infarct size, neurological outcomes, blood�brain barrier (BBB) permeability, apoptosis and brain-derived neurotrophic factor (BDNF) expression in a mouse model of stroke. Transient focal cerebral ischemia was established by middle cerebral artery occlusion (MCAO) for 45 min and followed reperfusion for 23 h in mice. Recombinant irisin was administrated at doses of 0.1, 0.5, 2.5, 7.5, and 15 µg/kg, intracerebroventricularly (ICV), on the MCAO beginning. Neurological outcomes, infarct size, brain edema and BBB permeability were evaluated by modified neurological severity score (mNSS), 2,3,5-triphenyltetrazolium chloride (TTC) staining and Evans blue (EB) extravasation methods, respectively, at 24 h after ischemia. Apoptotic cells and BDNF protein were detected by TUNEL assay and immunohistochemistry techniques. The levels of Bcl-2, Bax and caspase-3 proteins were measured by immunoblotting technique. ICV irisin administration at doses of 0.5, 2.5, 7.5 and 15 µg/kg, significantly reduced infarct size, whereas only in 7.5 and 15 µg/kg improved neurological outcome (P < 0.001). Treatment with irisin (7.5 µg/kg) reduced brain edema (P < 0.001) without changing BBB permeability (P > 0.05). Additionally, irisin (7.5 µg/kg) significantly diminished apoptotic cells and increased BDNF immunoreactivity in the ischemic brain cortex (P < 0.004). Irisin administration significantly downregulated the Bax and caspase-3 expression and upregulated the Bcl-2 protein. The present study indicated that irisin attenuates brain damage via reducing apoptosis and increasing BDNF protein of brain cortex in the experimental model of stroke in mice. © 2018, Springer Science+Business Media, LLC, part of Springer Nature.

Item Type: Article
Additional Information: cited By 1
Uncontrolled Keywords: brain derived neurotrophic factor; caspase 3; irisin; protein Bax; protein bcl x; recombinant irisin; recombinant protein; unclassified drug, animal experiment; animal model; animal tissue; apoptosis; Article; blood brain barrier; brain blood flow; brain circulation; brain cortex; brain edema; brain infarction size; brain ischemia; brain protection; cerebrovascular accident; controlled study; disease severity assessment; dose response; down regulation; drug dose comparison; drug mechanism; extravasation; immunoblotting; male; membrane permeability; middle cerebral artery occlusion; motor performance; mouse; mouse model; nonhuman; priority journal; protein expression; rodent model; scoring system; sensation; treatment outcome; upregulation
Subjects: WL Nervous System
Depositing User: eprints admin
Date Deposited: 30 Dec 2018 09:35
Last Modified: 21 Aug 2019 10:12

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