Transplantation of cultured choroid plexus epithelial cells via cerebrospinal fluid shows prominent neuroprotective effects against acute ischemic brain injury in the rat

• Published in: Neuroscience letters 2010-01, Vol.469 (3), p.283-288
• Main Authors: Matsumoto, Naoya, Taguchi, Akihiko, Kitayama, Hitoshi, Watanabe, Yumi, Ohta, Masayoshi, Yoshihara, Tomoyuki, Itokazu, Yutaka, Dezawa, Mari, Suzuki, Yoshihisa, Sugimoto, Hisashi, Noda, Makoto, Ide, Chizuka
• Format: Article
• Language: English
• Subjects: Animals; Apoptosis; Biological and medical sciences; Brain - pathology; Brain - physiopathology; Brain Ischemia - pathology; Brain Ischemia - physiopathology; Brain Ischemia - therapy; Brain Tissue Transplantation - methods; Cell transplantation; Cells, Cultured; Cerebral circulation. Blood-brain barrier. Choroid plexus. Cerebrospinal fluid. Circumventricular organ. Meninges; Cerebrospinal Fluid; Choroid Plexus - cytology; Choroid plexus epithelial cell; Epithelial Cells - transplantation; Fourth Ventricle - physiopathology; Fundamental and applied biological sciences. Psychology; Infarction, Middle Cerebral Artery - pathology; Infarction, Middle Cerebral Artery - physiopathology; Infarction, Middle Cerebral Artery - therapy; Ischemic brain injury; Male; Medical sciences; Neuroimmunomodulation; Neurology; Neuroprotection; Rats; Rats, Wistar; RNA, Messenger - metabolism; Treatment Outcome; Vascular diseases and vascular malformations of the nervous system; Vertebrates: nervous system and sense organs
• ISSN: 0304-3940; 1872-7972
• DOI: 10.1016/j.neulet.2009.09.060

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.