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星形胶质细胞动力学药物治疗神经退行性疾病的概念:L-司来吉兰诱导反应性星形胶质细胞活化的证据

The concept of astrocyte-kinetic drug in the treatment of neurodegenerative diseases: evidence for L-deprenyl-induced activation of reactive astrocytes.

作者信息

Biagini G, Frasoldati A, Fuxe K, Agnati L F

机构信息

Institute of Human Physiology, University of Modena, Italy.

出版信息

Neurochem Int. 1994 Jul;25(1):17-22. doi: 10.1016/0197-0186(94)90047-7.

Abstract

Basic fibroblast growth factor (bFGF) increases neuronal survival and growth in cell cultures and stimulates functional recovery from brain lesion. In addition, bFGF is able to induce glial cell proliferation and differentiation. Recently, L-deprenyl has been shown to potentiate astrocyte reaction to a mechanical lesion and to possess a trophic-like activity in several experimental models. In the present paper, we have therefore investigated if the enhancing effect of L-deprenyl on astrocyte reactivity is accompanied by increased levels of bFGF. The effect of L-deprenyl (0.25 mg/kg/day) on bFGF immunoreactivity (IR) after the insertion of an injection cannula in rat neostriatum have been investigated. It has been found that subchronic L-deprenyl treatment potentiates both the lesion-induced increase of glial fibrillary acidic protein (GFAP) and bFGF IRs (P < 0.01). These data suggest that a possible mechanism for L-deprenyl-induced neuroprotection may be the activation of astrocytes associated with increased secretion of trophic factors that promote neuronal survival and growth. This "astrocyte-kinetic" action of L-deprenyl could represent a new therapeutical approach to increase trophic support of lesioned neurons.

摘要

碱性成纤维细胞生长因子(bFGF)可提高细胞培养中神经元的存活率和生长速度,并促进脑损伤后的功能恢复。此外,bFGF能够诱导神经胶质细胞的增殖和分化。最近研究表明,L-司来吉兰能增强星形胶质细胞对机械损伤的反应,并在多个实验模型中具有类似营养因子的活性。因此,在本文中,我们研究了L-司来吉兰对星形胶质细胞反应性的增强作用是否伴随着bFGF水平的升高。我们研究了L-司来吉兰(0.25mg/kg/天)对大鼠新纹状体插入注射套管后bFGF免疫反应性(IR)的影响。研究发现,亚慢性L-司来吉兰治疗可增强损伤诱导的胶质纤维酸性蛋白(GFAP)和bFGF IRs的增加(P<0.01)。这些数据表明,L-司来吉兰诱导神经保护的一种可能机制可能是星形胶质细胞的激活,同时伴随着促进神经元存活和生长的营养因子分泌增加。L-司来吉兰的这种“星形胶质细胞动力学”作用可能代表了一种增加损伤神经元营养支持的新治疗方法。

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