PMID- 31672459 OWN - NLM STAT- MEDLINE DCOM- 20200914 LR - 20211204 IS - 1873-6300 (Electronic) IS - 0891-0618 (Linking) VI - 102 DP - 2019 Dec TI - Conditioned medium obtained from human amniotic mesenchymal stem cells attenuates focal cerebral ischemia/reperfusion injury in rats by targeting mTOR pathway. PG - 101707 LID - S0891-0618(19)30118-8 [pii] LID - 10.1016/j.jchemneu.2019.101707 [doi] AB - Conditioned medium obtained from human amniotic mesenchymal stem cells (hAMSC-CM) was recently shown to have many antioxidant, antiapoptotic and proangiogenic growth factors. The present study was performed to investigate whether protective effects of hAMSC-CM against focal cerebral ischemia/ reperfusion (I/R) injury is associated with modulation of the mammalian target of rapamycin (mTOR) pathway. A rat model of middle cerebral artery occlusion (MCAO) was created and the animals were divided into three groups including sham, MCAO and MCAO + hAMSC-CM. Drug was administrated immediately after cerebral reperfusion (i.v). The expressions of mTOR, p-mTOR and LC3 were measured using Western blotting and real time-PCR, respectively. Apoptosis and neuronal loss were determined using TUNEL and Nissl staining, respectively. Infarct volume and the blood-brain barrier (BBB) damage were evaluated using 2,3,5-triphenyltetrazolium chloride (TTC) staining and Evans Blue (EB) uptake, respectively. Compared with sham, significant infarct volume, apoptotic cell death, and neuronal loss were found in MCAO rats that reversed by hAMSC-CM (P < 0.05). Likewise, MCAO rats exhibited increased mRNA level of light-chain 3 (LC3) and the LC3II/LC3I ratio as well as decreased expression level of p-mTOR that reversed by hAMSC-CM (P < 0.05). There were no significant differences in the expression of total mTOR among the experimental groups. In summary, our results demonstrate that hAMSC-CM gives rise to neuroprotection following ischemic stroke by restoring mTOR activity and inhibiting autophagy. CI - Copyright (c) 2019 Elsevier B.V. All rights reserved. FAU - Nazarinia, Donya AU - Nazarinia D AD - Physiology Research Center and Department of Physiology, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran. FAU - Aboutaleb, Nahid AU - Aboutaleb N AD - Physiology Research Center and Department of Physiology, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran. Electronic address: Aboutaleb.n@iums.ac.ir. FAU - Gholamzadeh, Raheleh AU - Gholamzadeh R AD - Physiology Research Center and Department of Physiology, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran. FAU - Nasseri Maleki, Solmaz AU - Nasseri Maleki S AD - Physiology Research Center and Department of Physiology, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran. FAU - Mokhtari, Behnaz AU - Mokhtari B AD - Physiology Research Center and Department of Physiology, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran. FAU - Nikougoftar, Mahin AU - Nikougoftar M AD - Blood Transfusion Research Center, High Institute for Research and Education in Transfusion Medicine, Tehran, Iran. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20191028 PL - Netherlands TA - J Chem Neuroanat JT - Journal of chemical neuroanatomy JID - 8902615 RN - 0 (Culture Media, Conditioned) RN - EC 2.7.11.1 (TOR Serine-Threonine Kinases) SB - IM MH - Amnion/*cytology MH - Animals MH - Apoptosis/drug effects MH - Blood-Brain Barrier/metabolism MH - Brain/metabolism MH - Brain Ischemia/*drug therapy/metabolism MH - Culture Media, Conditioned/*pharmacology MH - Humans MH - Male MH - Mesenchymal Stem Cells/*cytology MH - Rats MH - Rats, Wistar MH - Reperfusion Injury/*drug therapy/metabolism MH - Signal Transduction/*drug effects MH - TOR Serine-Threonine Kinases/*metabolism OTO - NOTNLM OT - Autophagy OT - Conditioned medium OT - Focal cerebral ischemia reperfusion injury OT - Mesenchymal stem cells OT - mTOR activity EDAT- 2019/11/02 06:00 MHDA- 2020/09/15 06:00 CRDT- 2019/11/02 06:00 PHST- 2019/07/02 00:00 [received] PHST- 2019/10/22 00:00 [revised] PHST- 2019/10/23 00:00 [accepted] PHST- 2019/11/02 06:00 [pubmed] PHST- 2020/09/15 06:00 [medline] PHST- 2019/11/02 06:00 [entrez] AID - S0891-0618(19)30118-8 [pii] AID - 10.1016/j.jchemneu.2019.101707 [doi] PST - ppublish SO - J Chem Neuroanat. 2019 Dec;102:101707. doi: 10.1016/j.jchemneu.2019.101707. Epub 2019 Oct 28.