PMID- 29882126 OWN - NLM STAT- MEDLINE DCOM- 20190401 LR - 20190401 IS - 1573-6903 (Electronic) IS - 0364-3190 (Linking) VI - 43 IP - 8 DP - 2018 Aug TI - Irisin Peptide Protects Brain Against Ischemic Injury Through Reducing Apoptosis and Enhancing BDNF in a Rodent Model of Stroke. PG - 1549-1560 LID - 10.1007/s11064-018-2569-9 [doi] AB - 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 microg/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 microg/kg, significantly reduced infarct size, whereas only in 7.5 and 15 microg/kg improved neurological outcome (P < 0.001). Treatment with irisin (7.5 microg/kg) reduced brain edema (P < 0.001) without changing BBB permeability (P > 0.05). Additionally, irisin (7.5 microg/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. FAU - Asadi, Yasin AU - Asadi Y AD - Research Center and Department of Physiology, Faculty of Medicine, Semnan University of Medical Sciences, Semnan, Iran. FAU - Gorjipour, Fazel AU - Gorjipour F AD - Physiology Research Center, Iran University of Medical Sciences, Tehran, Iran. FAU - Behrouzifar, Sedigheh AU - Behrouzifar S AD - Research Center and Department of Physiology, Faculty of Medicine, Semnan University of Medical Sciences, Semnan, Iran. FAU - Vakili, Abedin AU - Vakili A AUID- ORCID: 0000-0002-4269-9978 AD - Research Center and Department of Physiology, Faculty of Medicine, Semnan University of Medical Sciences, Semnan, Iran. Ab.vakili@yahoo.com. LA - eng GR - 917/Vice Chancellor for Research of the Semnan University of Medical Sciences/ PT - Journal Article DEP - 20180607 PL - United States TA - Neurochem Res JT - Neurochemical research JID - 7613461 RN - 0 (Bax protein, mouse) RN - 0 (Bdnf protein, mouse) RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (FNDC5 protein, mouse) RN - 0 (Fibronectins) RN - 0 (Proto-Oncogene Proteins c-bcl-2) RN - 0 (Recombinant Proteins) RN - 0 (bcl-2-Associated X Protein) RN - 114100-40-2 (Bcl2 protein, mouse) RN - EC 3.4.22.- (Casp3 protein, mouse) RN - EC 3.4.22.- (Caspase 3) SB - IM MH - Animals MH - Apoptosis/*drug effects MH - Blood-Brain Barrier/drug effects MH - Brain Edema/prevention & control MH - Brain-Derived Neurotrophic Factor/*metabolism MH - Caspase 3/genetics MH - Dose-Response Relationship, Drug MH - Down-Regulation/drug effects MH - Fibronectins/pharmacology/*therapeutic use MH - Infarction, Middle Cerebral Artery/*drug therapy MH - Male MH - Mice MH - Proto-Oncogene Proteins c-bcl-2/genetics MH - Recombinant Proteins/pharmacology/therapeutic use MH - Time Factors MH - Up-Regulation/genetics MH - bcl-2-Associated X Protein/genetics OTO - NOTNLM OT - Apoptosis OT - BDNF OT - Blood-brain barrier permeability OT - Brain edema OT - Focal cerebral ischemia OT - Immunohistochemistry OT - Infarct size OT - Mice EDAT- 2018/06/09 06:00 MHDA- 2019/04/02 06:00 CRDT- 2018/06/09 06:00 PHST- 2018/04/09 00:00 [received] PHST- 2018/06/04 00:00 [accepted] PHST- 2018/05/29 00:00 [revised] PHST- 2018/06/09 06:00 [pubmed] PHST- 2019/04/02 06:00 [medline] PHST- 2018/06/09 06:00 [entrez] AID - 10.1007/s11064-018-2569-9 [pii] AID - 10.1007/s11064-018-2569-9 [doi] PST - ppublish SO - Neurochem Res. 2018 Aug;43(8):1549-1560. doi: 10.1007/s11064-018-2569-9. Epub 2018 Jun 7.