Jana Malabendu, Jana Arundhati, Pal Utpal, Pahan Kalipada
Department of Neurological Sciences, Rush University Medical Center, Chicago, IL 60612, USA.
Neurochem Res. 2007 Dec;32(12):2015-22. doi: 10.1007/s11064-007-9340-y. Epub 2007 Apr 20.
Elucidation of the underlying pathogenic mechanisms leading to apoptosis of neurons and oligodendrocytes and activation of microglia and astrocytes in different neurodegenerative and neuroinflammatory disorders remains a challenge in neuroscience. In order to overcome the challenge and find out therapeutic remedies, it is important to study live and death processes in each and every cell type of the brain. Here we present a protocol of isolating highly purified microglia, astrocytes, oligodendrocytes, and neurons, all four major cell types of the CNS, from the same human fetal brain tissue. As found in vivo, these primary neurons and oligodendroglia underwent apoptosis and cell death in response to neurodegenerative challenges. On the other hand, astroglia, and microglia, cells that do not die in neurodegenerative brains, became activated after inflammatory challenge. The availability of highly purified human brain cells will increase the possibility of developing therapies for different neurodegenerative disorders.
阐明导致不同神经退行性疾病和神经炎症性疾病中神经元和少突胶质细胞凋亡以及小胶质细胞和星形胶质细胞激活的潜在致病机制仍是神经科学领域的一项挑战。为了克服这一挑战并找到治疗方法,研究大脑中每种细胞类型的生死过程非常重要。在此,我们展示了一种从同一人类胎儿脑组织中分离出高度纯化的小胶质细胞、星形胶质细胞、少突胶质细胞和神经元(中枢神经系统的所有四种主要细胞类型)的方案。正如在体内所发现的那样,这些原代神经元和少突胶质细胞在面对神经退行性挑战时会发生凋亡和细胞死亡。另一方面,星形胶质细胞和小胶质细胞,即在神经退行性大脑中不会死亡的细胞,在受到炎症挑战后会被激活。高度纯化的人类脑细胞的可得性将增加开发针对不同神经退行性疾病疗法的可能性。