PMID- 24292945 OWN - NLM STAT- MEDLINE DCOM- 20140725 LR - 20240323 IS - 0219-1032 (Electronic) IS - 1016-8478 (Print) IS - 1016-8478 (Linking) VI - 36 IP - 6 DP - 2013 Dec TI - Administration of mesenchymal stem cells and ziprasidone enhanced amelioration of ischemic brain damage in rats. PG - 534-41 LID - 10.1007/s10059-013-0235-2 [doi] AB - Ziprasidone is a benzisothiazolyl piperazine derivative that was developed from the chemically related antipsychotic drug tiospirone, and it improves neurological functions of the ischemic brain and is effective in treatment of schizophrenia. Mesenchymal stem cells (MSCs) are considered as a leading candidate for neurological regenerative therapy because of their neural differentiation properties in damaged brain. We investigated whether the transplantation of neural progenitor cells (NPCs) derived from adipose mesenchymal stem cells combined with ziprasidone enhances neuroprotective effects in an animal model of focal cerebral ischemia. In combination therapy groups, significant reduction of infarct volume and improvement of neurological functions were observed at 3 days after middle cerebral artery occlusion (MCAO) compared with monotherapy. Co-administration of ziprasidone and NPCs enhanced the anti-apoptotic effect and reduced the number of terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)-positive apoptotic cells compared with the NPCs alone group at 7 days after MCAO. Ziprasidone or the combination of ziprasidone and NPCs induced the expression of endogenous neurotrophic factor gene brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), and glial cell-derived neurotrophic factor (GDNF). The immunohistochemical investigation revealed that the ziprasidone and NPCs attenuated the increased intensity of microglial marker (Iba-1) in the infarcted cortical area. Moreover, the number of transplanted NPCs on day 7 with combination therapy was significantly higher than with NPCs alone. These effects might be responsible for improved functional behavior and increased survival of NPCs. Our finding indicates that combination therapy of ziprasidone and NPCs enhances neuroprotection against ischemic brain injury. FAU - Kaengkan, Phatcharida AU - Kaengkan P AD - Department of Biological Sciences, Institute of Basic Science, Inje University, Gimhae, 621-749, Korea. FAU - Baek, Seung Eun AU - Baek SE FAU - Kim, Ji Yeong AU - Kim JY FAU - Kam, Kyung-Yoon AU - Kam KY FAU - Do, Byung-Rok AU - Do BR FAU - Lee, Eun Shin AU - Lee ES FAU - Kang, Sung Goo AU - Kang SG LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20131128 PL - United States TA - Mol Cells JT - Molecules and cells JID - 9610936 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Glial Cell Line-Derived Neurotrophic Factor) RN - 0 (Neuroprotective Agents) RN - 0 (Piperazines) RN - 0 (Thiazoles) RN - 6UKA5VEJ6X (ziprasidone) RN - 9061-61-4 (Nerve Growth Factor) SB - IM MH - Animals MH - Brain Ischemia/physiopathology/*therapy MH - Brain-Derived Neurotrophic Factor/metabolism MH - Cell Survival/drug effects MH - Combined Modality Therapy MH - Disease Models, Animal MH - Gene Expression Regulation MH - Glial Cell Line-Derived Neurotrophic Factor/metabolism MH - Humans MH - Male MH - *Mesenchymal Stem Cell Transplantation MH - Mesenchymal Stem Cells/*metabolism MH - Microglia/drug effects MH - Nerve Growth Factor/metabolism MH - Neural Stem Cells/*transplantation MH - Neuroprotective Agents/*administration & dosage/pharmacology MH - Piperazines/*administration & dosage/pharmacology MH - Rats MH - Rats, Sprague-Dawley MH - Thiazoles/*administration & dosage/pharmacology PMC - PMC3887965 EDAT- 2013/12/03 06:00 MHDA- 2014/07/26 06:00 PMCR- 2014/12/31 CRDT- 2013/12/03 06:00 PHST- 2013/08/22 00:00 [received] PHST- 2013/11/04 00:00 [accepted] PHST- 2013/10/25 00:00 [revised] PHST- 2013/12/03 06:00 [entrez] PHST- 2013/12/03 06:00 [pubmed] PHST- 2014/07/26 06:00 [medline] PHST- 2014/12/31 00:00 [pmc-release] AID - S1016-8478(23)05186-5 [pii] AID - molcell-36-6-534-6 [pii] AID - 10.1007/s10059-013-0235-2 [doi] PST - ppublish SO - Mol Cells. 2013 Dec;36(6):534-41. doi: 10.1007/s10059-013-0235-2. Epub 2013 Nov 28.