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

脉络膜丛（CP）通过提供脑脊液（CSF）为大脑提供适当的环境。然而，CP在大脑中的生理功能尚未被揭示。培养的脉络膜丛上皮细胞（CPECs）经第4脑室输注脑脊液抗大鼠大脑中动脉闭塞模型，可保护梗死灶扩张，抑制细胞凋亡、炎症和氧化应激。移植细胞留在脑室内，在缺血灶中未发现。这一事实表明，多种来自移植细胞的分泌因子通过脑脊液发挥神经保护的营养作用。使用transwell对cpec与神经元或内皮细胞之间的非接触共培养系统进行的研究支持了这一推测。cpec的存在a)促进神经突延伸，b)抑制神经元细胞死亡，c)增强内皮细胞的存活。此外，我们还发现cpec分泌的部分神经营养或再生因子参与了捕获超过50kD的蛋白/肽。CP可能通过调节中枢神经系统的微环境，向脑脊液提供各种营养因子，在脑功能维持中发挥关键作用。在cpec中增强分泌诱导的转录因子对缺血性脑损伤的影响，促进神经保护和神经发生，调节脑脊液的不良环境，是一种有前景的新策略。

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.