103 J Contemp Med Sci | Vol. 6, No. 3, May–June 2020: 103–108 Original ISSN 2413-0516 Introduction Stroke is the most prevalent vascular accident of central ner- vous system among middle aged individuals. Te sensory- motor dysfunction, cognitive impairments, and declined quality of life are the side efects of stroke in sufered patients. 1 Unfortunately, no efective pharmaceutical treatment has been introduced, only endovascular approaches or rehabilitation may reduce the severity of symptoms. 2 In the feld of regen- erative medicine, there are numerous preclinical and clinical studies that demonstrated the therapeutic efect of stem cell transplantation in various neurodegenerative diseases such as ischemic stroke. 3-5 Embryonic stem cells (ESC), the plu- ripotent stem cells, can diferentiate to diferent lineages. So that, under defned protocol, embryonic stem cells has been shown to diferentiate to neural progenitor cells (NPC). 6 Afer transplantation of embryonic derived neural progenitor cells (ES-NPCs) in model of middle cerebral artery occlusion (MCAO) in the rats, the cells are capable to migrate toward ischemic site, proliferate and diferentiate to the neurons and glial cells, and replace the dead cells. 7 On the other hand, they induce angiogenesis and neurogenesis, decrease the neuroin- fammation, and preserve the integrity of blood–brain barrier through bystander efects. 8 Following the ES-NPCs injection, the size of ischemic area reduced and the sensory-motor func- tion improved. Te histological investigation also revealed positive fndings in favor of neural tissue repair. 6, 9, 10 Moreover, diferent types of biomarkers such as micro- RNAs (miRNAs) appear in blood and brain tissue fol- lowing ischemia. Te miRNAs are small non-coding and single-stranded RNAs that regulate many internal processes such as cell proliferation, diferentiation, development, cell cycle, apoptosis, etc. In addition to tissues, they are present in serum or plasma in the form of complexes and macroves- icles. 11 Te previous studies exposed that a wide spectrum of miRNAs identifed, in the blood and brain tissue afer MCAO in rats by microarray with both up- and downregulated man- ner. Clinical studies also confrmed these fndings in patients with ischemic stroke. Terefore, the miRNAs are considered as a promising biomarker for prognosis of stroke patients. 12-16 miRNA-210 has been shown to prevent neuronal apopto- sis and with neuroprotective role by suppressing the caspase pathway, induce a balance between bcl-2 and bax expres- sion. 17 In ischemic condition, mir-210 plays role as a proan- giogenic factor and involves in cell-cycle regulation, DNA damage reconstruction, and neural tissue restoration. 17-19 Human embryonic derived neural progenitor cells improves neurological scores following brain ischemia/ reperfusion: Modulation of blood and brain tissue MicroRNA-210 Leila Arab 1 , Aslan Fanni 2 , Shiva Nemati #2 , Ehsan Arefan 3 , Jafar Ai #4 , Tahmineh Mokhtari 5,6 , Maryam Farahmandfar 7 , Nasser Aghdami 2 , Gholamreza Hassanzadeh 1,8,9 1 Department of Neuroscience and Addiction Studies, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran. 2 Department of Stem cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran. 3 Department of Microbiology, School of Biology College of Science, University of Tehran, Tehran, Iran. 4 Department of Tissue Engineering and Applied Cell Sciences, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran. 5 CAS Key Laboratory of Mental Health, Institute of Psychology, Beijing, China; 6 Department of Psychology, University of Chinese Academy of Sciences, Beijing, China 7 Department of Neuroscience and Addiction Studies, School of Advanced Technologies in Medicine, Electrophysiology Research Center, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran. 8 Legal Medicine Research Center, Legal Medicine Organization, Tehran, Iran. 9 Department of Anatomy, School of Medicine, Tehran University of Medical Science, Tehran, Iran. #2 co-second author #3 co-third author Correspondence to: Gholamreza Hassanzadeh (hassanzadeh@tums.ac.ir ) (Submitted: 13 March 2020 – Revised version received: 28 March 2020 – Accepted: 11 May 2020 – Published online: 26 June 2020) Objective In this study, we evaluated the efects of human embryonic derived neural progenitor cells on neurological score, histopathological changes, and miRNA-210 as biomarkers of regeneration. Methods The animals were randomly divided into the four groups: Sh (sham), MCAO (middle cerebral artery occlusion), MCAO+PBS, and MCAO+Cell. One day after MCAO induction, embryonic derived neural progenitor cells (hESC-NPCs GFP ) or PBS were injected intracerebroventriculary in MCAO+Cell or MCAO+PBS groups. On day 1, 2, 3, and 7 after ischemia induction, the neurological score was tested in each rat. At 48 h, the expression of miRNA-210 was evaluated and 7 days after, the pathological assessments were performed by H&E staining. Results Neurological score showed the promotion of functional recovery in MCAO+Cell group. Based on H&E staining, the percentage of neural death in ischemic region reduced in MCAO+Cell group. The miRNA-210 signifcantly upregulated in both brain and blood samples. Conclusion According to the fndings, hESC-NPCs GFP injection could upregulate the miRNA-210 of tissue and blood to support the neuroprotective and regenerative efect of hESC-NPCs GFP in the ischemic lesion and improved the neurological score and reduce the neural death in ischemic region. Keywords Embryonic stem cell; Neural death; Micro-RNA-210; Brain ischemia; Rat