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

脉络丛(CP)通过供应脑脊液(CSF)为大脑提供适当的环境。然而，CP在大脑中的生理功能还没有被发现。将培养的脉络丛上皮细胞(CPECs)通过第四脑室注入脑脊液，可保护脑梗塞扩大，抑制细胞凋亡、炎症反应和氧化应激。移植细胞仍留在脑室内，缺血灶内未见。这一事实表明，移植细胞来源的多种分泌因子通过脑脊液对神经保护起营养作用。使用Transwell对CPECs和神经元或内皮细胞之间的非接触性共培养系统的研究支持了这一推测。CPECs的存在a)促进轴突延伸，b)抑制神经细胞死亡，c)增加内皮细胞的存活。此外，还证实CPECs分泌的部分神经营养因子或再生因子参与了截留50kD以上的蛋白质/多肽。CP可能通过调节中枢神经系统微环境，为脑脊液提供多种营养因子，在脑功能维持中发挥重要作用。增强促分泌剂诱导的转录因子在CPECs抗缺血性脑损伤中的作用，将促进神经保护和神经再生，调节脑脊液的不利环境，成为一种新的有前景的策略。

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.