PMID- 30171723 OWN - NLM STAT- MEDLINE DCOM- 20191202 LR - 20200204 IS - 1097-4644 (Electronic) IS - 0730-2312 (Linking) VI - 119 IP - 12 DP - 2018 Dec TI - Comparison between the effect of human Wharton's jelly-derived mesenchymal stem cells and levetiracetam on brain infarcts in rats. PG - 9790-9800 LID - 10.1002/jcb.27297 [doi] AB - BACKGROUND: Stroke represents one of the major causes of death worldwide. Neuroprotection remains an important goal of stroke therapy. Stem cell therapeutic effect is attributed to the neuroprotective effect and the regulation of the oxidant stress. Levetiracetam (LEV), a second-generation antiepileptic drug, was reported to confer neuronal protection after cerebral ischemia reperfusion. AIM: To investigate the effect of human Wharton's jelly-derived mesenchymal stem cells (WJ-MSCs) and LEV on the size of brain infarcts, the histological structure, the neurotrophic, and the antioxidant gene expression in middle cerebral artery occlusion in rats. METHOD: The rats were divided into five equal groups of 12 rats each as follows. Sham control group: received phosphate-buffered saline (PBS); ischemia/reperfusion (I/R) group: received PBS before ligation; stem cell-treated group: the animal received MSCs before ligation; LEV-treated group: the animal received LEV before occlusion; combined group: the animals received both MSCs and LEV before occlusion. Hematoxylin and eosin staining was performed to study the histological structure of the brain. Real-time polymerase chain reaction (RT-PCR) was performed to assess gene expression. RESULTS: Both MSCs and LEV improved memory and learning in the treated groups compared with I/R group. Significant reduction of the infarct size in WJ-MSC- or LEV-treated groups when compared with untreated ones was found. By RT-PCR, a significant decrease of the expression values of glial-derived neurotrophic factor (GDNF), brain-derived neurotrophic factor (BDNF), phosphatidylethanolamine binding protein 1 (PEBP1), and copper-zinc SOD (Cu/ZnSOD) genes and a significant increase of pro-oxidant iNOS gene in the I/R rats compared with the sham group was detected. There was a significant increase in the expression values of GDNF, BDNF, PEBP1, and Cu/ZnSOD genes in both treated groups when compared with the I/R group. Rats treated with WJ-MSCs showed better results than rats treated with LEV. Finally, the combined use of LEV and WJ-MSCs was the most effective regimen as regard infarction volume and functional learning and memory tests. CONCLUSION: In the brain ischemia model, combined WJ-MSCs and LEV have demonstrated striking protective effects in brain infarction by the modulation of the oxidant status and neuroprotective effect. CI - (c) 2018 Wiley Periodicals, Inc. FAU - Abd El Motteleb, Dalia M AU - Abd El Motteleb DM AD - Pharmacology Department, Faculty of Medicine, Zagazig University, Zagazig, Egypt. FAU - Hussein, Samia AU - Hussein S AUID- ORCID: 0000-0002-7407-1608 AD - Medical Biochemistry and Molecular Biology Department, Faculty of Medicine, Zagazig University, Zagazig, Egypt. FAU - Hasan, Mai M AU - Hasan MM AD - Medical Physiology Department, Faculty of Medicine, Zagazig University, Zagazig, Egypt. FAU - Mosaad, Hala AU - Mosaad H AD - Medical Biochemistry and Molecular Biology Department, Faculty of Medicine, Zagazig University, Zagazig, Egypt. LA - eng PT - Comparative Study PT - Journal Article DEP - 20180901 PL - United States TA - J Cell Biochem JT - Journal of cellular biochemistry JID - 8205768 RN - 0 (Bdnf protein, rat) RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (GFAP protein, rat) RN - 0 (Glial Cell Line-Derived Neurotrophic Factor) RN - 0 (Glial Fibrillary Acidic Protein) RN - 0 (Neuroprotective Agents) RN - 0 (PEBP1 protein, rat) RN - 0 (Phosphatidylethanolamine Binding Protein) RN - 44YRR34555 (Levetiracetam) RN - EC 3.4.22.- (Casp3 protein, rat) RN - EC 3.4.22.- (Caspase 3) SB - IM MH - Animals MH - Brain Infarction/metabolism/pathology/*therapy MH - Brain-Derived Neurotrophic Factor/genetics MH - Caspase 3/metabolism MH - Gene Expression MH - Glial Cell Line-Derived Neurotrophic Factor/genetics MH - Glial Fibrillary Acidic Protein/metabolism MH - Humans MH - Learning/drug effects/physiology MH - Levetiracetam/*pharmacology MH - Male MH - Memory/drug effects/physiology MH - Mesenchymal Stem Cell Transplantation/*methods MH - Neuroprotective Agents/*pharmacology MH - Phosphatidylethanolamine Binding Protein/genetics MH - Rats MH - Wharton Jelly/*cytology OTO - NOTNLM OT - Wharton's jelly-derived mesenchymal stem cells (WJ-MSCs) OT - brain infarction OT - levetiracetam (LEV) OT - middle cerebral artery occlusion (MCAO) OT - real-time polymerase chain reaction (RT-PCR) EDAT- 2018/09/02 06:00 MHDA- 2019/12/04 06:00 CRDT- 2018/09/02 06:00 PHST- 2017/11/23 00:00 [received] PHST- 2018/06/26 00:00 [accepted] PHST- 2018/09/02 06:00 [pubmed] PHST- 2019/12/04 06:00 [medline] PHST- 2018/09/02 06:00 [entrez] AID - 10.1002/jcb.27297 [doi] PST - ppublish SO - J Cell Biochem. 2018 Dec;119(12):9790-9800. doi: 10.1002/jcb.27297. Epub 2018 Sep 1.