The identification of transcription factors which induce the secretion of neurotrophic factores in choroid plexus epithelial cells.-Aming at the application to the therapy for cerebral infarction by gene delivery of the transcription factor

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The choroid plexus (CP) provides a proper environment for the brain by supplying cerebrospinal fluid (CSF). The physiological function of CP in the brain, however, has not been uncovered yet. The infusion of cultured choroid plexus epithelial cells (CPECs) into CSF through the 4th ventricle against rat middle cerebral artery occlusion model protected the infarct expansion, suppressing apoptosis, inflammation and oxidative stress. The transplanted cells remained inside the ventricle and could not been found in the ischemic foci. This fact suggested that a variety of secreted factors derived from transplanted cells exerted trophic effects on neuroprotection via CSF. This speculation was supported by a study of the non-contact coculture system between CPECs and neurons or endothelial cells using transwell. The presence of CPECs a) promoted neurite extension, b) suppressed neuronal cell death, and c) augmented survival of endothelial cells. Furthermore, it was demonstrated that a part of neurotorphic or regenerative factors secreted from CPECs were involved in proteins/peptides which seize was more than 50kD. CP may play a crucial role in functional maintenance of the brain by regulating the microenvironmet of the central nervous system, by supplying a various trophic factors into CSF. The enhancement of secretagogue-induced transcriptional factors in CPECs against ischemic brain injury would promote the neuroprotection and neurogenesis, adjusting the CSF adverse environment, and become a new promising strategy.