Wang Wei, Redecker Christoph, Yu Zhi-Yuan, Xie Min-Jie, Tian Dai-Shi, Zhang Liang, Bu Bi-Tao, Witte Otto W
Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, PR China.
J Clin Neurosci. 2008 Mar;15(3):278-85. doi: 10.1016/j.jocn.2007.02.004. Epub 2008 Jan 22.
Astroglial proliferation and delayed neuronal death are two common pathological processes in the ischemic brain. However, it is not clear if astrogliosis causes delayed neuronal death. In this study, we addressed this potential linkage by examining the relationship between attenuated astrocyte proliferation, induced by cyclin-dependent kinase (CDK) inhibition, and delayed neuronal death in rat ischemic hippocampus. Our results show that following middle cerebral artery occlusion (MCAO), astrocyte hypertrophy and proliferation were closely associated with delayed neuronal death. Importantly, administration of olomoucine, a selective CDK inhibitor, not only suppressed astroglial proliferation and glial scar formation, but also decreased neuronal cell death in the ischemic boundary zone and hippocampal CA1 region at days 1 and 30 after MCAO. These results indicate that reactive astrogliosis and delayed neuronal death, at least in rat hippocampus, are sequential pathological events following MCAO. Therefore, suppressing astroglial cell cycle progression in acute focal cerebral ischemia may be beneficial to neuronal survival. Our study also implies that cell cycle regulation should be considered as a promising future therapeutic intervention in treating those neurological diseases characterized by an excessive astrocyte proliferation.
星形胶质细胞增生和迟发性神经元死亡是缺血性脑损伤中两个常见的病理过程。然而，尚不清楚星形胶质细胞增生是否会导致迟发性神经元死亡。在本研究中，我们通过研究细胞周期蛋白依赖性激酶（CDK）抑制诱导的星形胶质细胞增生减弱与大鼠缺血性海马中迟发性神经元死亡之间的关系，探讨了这种潜在联系。我们的结果表明，大脑中动脉闭塞（MCAO）后，星形胶质细胞肥大和增生与迟发性神经元死亡密切相关。重要的是，给予选择性CDK抑制剂olomoucine，不仅抑制了星形胶质细胞增生和胶质瘢痕形成，而且在MCAO后第1天和第30天减少了缺血边界区和海马CA1区的神经元细胞死亡。这些结果表明，至少在大鼠海马中，反应性星形胶质细胞增生和迟发性神经元死亡是MCAO后的连续病理事件。因此，在急性局灶性脑缺血中抑制星形胶质细胞的细胞周期进程可能有利于神经元存活。我们的研究还表明，细胞周期调控应被视为治疗那些以星形胶质细胞过度增生为特征的神经疾病的一种有前景的未来治疗干预措施。
