脑损伤具有致死、致残率高，恢复缓慢的特点。星形胶质细胞（AS）是中枢神经系统脑细胞中比例最多的细胞。 近年发现，AS在神经系统的生理和病理功能中均扮演不可取代的角色。本实验室一直以来研究AS在脑损伤和病变中的激活机制。激活的AS在受损处发生胶质化三部曲 - 细胞肥大，GFAP上调及细胞增生。本实验室已对在前两阶段进行了深入系统的研究。以此为基础，本项目将扩展AS胶质化的研究到第三阶段AS增生的发生机制。我们发现增生中存在对称和不对称两种细胞分裂。本项目将从细胞肥大早期观察到的细胞内部和膜上的多个极性表现包括钙信号、pH值、巨胞饮等的结果跟踪、阐明这些现象是否与后续增生过程细胞对称或不对称分裂的命运有特异性关联，并试图澄清增生过程中是否有神经干细胞的产生。本项目将对AS胶质化第三部曲的机理作系统研究，更可能为神经系统损伤中干细胞的来源之谜找出答案，为实现脑损伤的修复提供依据。

Brain injury is the major cause for brain dysfunctions with high mortality, disability and slow recovery. Astrocytes are the greatest population among all brain cells and playing vital roles in CNS functions. They can be reactivated in various injuries and diseases to form scar and plaques. This process is also known as astrogliosis which features a trilogy of reactive astrocytes: hypertrophy, GFAP upregulation and hyperplasia. Our previous studies have unraveled some detailed mechanisms involved in the first two phases. The current project would extend our astrogliosis study into the hyperplastic phase, aiming to investigate whether our observation of cell polarity in the aspect of Ca2+ signal, changes of pH and macropinocytosis, etc. during the hypertrophic phase are related to the symmetrical or asymmetrical cell divisions during hyperplasia. The results from this study will further our knowledge on astrogliosis, thus would allow us to manipulate the mechanisms to derive means of modulating scar formation. Most important of all, our result might be able to clarify whether the asymmetrical cell division under hyperplasia in these injured astrocytes would be the source of stem cells as observed in many studies indicating astrocytes might be one of the origins of stem cells in injured brains. The current study would thus provide evidence for brain injury repair via an internal intrinsic way.