Transplantation of cultured choroid plexus epithelial cells via cerebrospinal fluid shows prominent neuroprotective effects against acute ischemic brain injury in the rat |
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| Authors: | Naoya Matsumoto Akihiko Taguchi Hitoshi Kitayama Yumi Watanabe Masayoshi Ohta Tomoyuki Yoshihara Yutaka Itokazu Mari Dezawa Yoshihisa Suzuki Hisashi Sugimoto Makoto Noda Chizuka Ide |
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| Affiliation: | 1. Department of Trauma and Acute Critical Care Center, Osaka University Hospital, 2-15 Yamadaoka, Suita, Osaka 565-0871, Japan;2. Department of Cerebrovascular Disease, National Cardiovascular Center, 5-7-1 Fujishiro-dai, Suita, Osaka 565-8565, Japan;3. Department of Molecular Oncology, Kyoto University Graduate School of Medicine, Yoshidakonoe-cho, Sakyo-ku, Kyoto 606-8501, Japan;4. Transdisciplinary Research Program, Graduate School of Medical and Dental Sciences, Niigata University, Niigata 951-8510, Japan;5. Department of Plastic and Reconstructive Surgery, Tazuke Medical Research Institute, Kitano Hospital, Osaka, Japan;6. Institute of Biomedicine, Department of Medical Biochemistry and Developmental Biology, University of Helsinki/Biomedicum Helsinki, Finland;g Department of Stem Cell Biology and Histology, Tohoku University Graduate School of Medicine, Sendai, Japan;h Department of Occupational Therapy, Faculty of Nursing and Rehabilitation, Institute of Regeneration and Rehabilitation, Aino University, Higashi-ohda 4-5-1, Ibaragi City, Osaka, Japan |
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| Abstract: | Choroid plexus (CP) epithelial cells (CPECs) produce cerebrospinal fluid (CSF) to provide the CNS with a specialized microenvironment. Our previous study showed that the conditioned medium of cultured CPECs enhanced the survival and neurite extension of hippocampal neurons. The present study examined the ability of cultured CPECs to protect against ischemic brain injury when transplanted into the CSF. Rats were subjected to a transient occlusion of the middle cerebral artery, followed by an injection of cultured CPECs into the fourth ventricle. The injection markedly reduced neurological deficits and infarction volume within 24 h. Other beneficial effects were (1) a reduction in number of apoptotic and inflammatory cells, (2) an up-regulation of the mRNA expression of an anti-apoptotic effecter, cAMP-response element binding protein, and (3) a down-regulation of the production of pro-inflammatory factors such as interleukin-1 beta and inducible nitric oxide synthase. The injected CPECs were located within the ventricles and on the brain's surface, not in the ischemic foci, suggesting that they exert their effects by releasing diffusible neuroprotective factors into the CSF. The transplantation of CPECs via CSF is a potential new strategy for protecting against ischemic brain injury. |
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| Keywords: | Choroid plexus epithelial cell Ischemic brain injury Cell transplantation Neuroprotection Cerebrospinal fluid |
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