Transplantation of cultured choroid plexus epithelial cells via cerebrospinal fluid shows prominent neuroprotective effects against acute ischemic brain injury in the rat.
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 24h. 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.
Department of Trauma and Acute Critical Care Center, Osaka University Hospital, 2-15 Yamadaoka, Suita, Osaka 565-0871, Japan. nao-m@hp-emerg.med.osaka-u.ac.jp
Naoya
N
Matsumoto
Akihiko
A
Taguchi
Hitoshi
H
Kitayama
Yumi
Y
Watanabe
Masayoshi
M
Ohta
Tomoyuki
T
Yoshihara
Yutaka
Y
Itokazu
Mari
M
Dezawa
Yoshihisa
Y
Suzuki
Hisashi
H
Sugimoto
Makoto
M
Noda
Chizuka
C
Ide
D000818:Animals; D017209:Apoptosis; D001921:Brain / Q000473:pathology / Q000503:physiopathology; D002545:Brain Ischemia / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D016380:Brain Tissue Transplantation / Q000379:methods*; D002478:Cells, Cultured; D002555:Cerebrospinal Fluid; D002831:Choroid Plexus / Q000166:cytology*; D004847:Epithelial Cells / Q000637:transplantation*; D020546:Fourth Ventricle / Q000503:physiopathology; D020244:Infarction, Middle Cerebral Artery / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D008297:Male; D015213:Neuroimmunomodulation; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D016896:Treatment Outcome
D012333:RNA, Messenger