Human Brain Slice Culture: A Useful Tool to Study Brain Disorders and Potential Therapeutic Compounds

摘要

Illustrations of human brain tissue in culture. Two pyramidal neurons stained with DiI (red) in a postmortem slice from a demented, non-AD patient after 50 days (DIV 50). After this long period the neuronal morphology is still intact. – Viability staining (Live/Dead, Molecular Probes) of postmortem slices from a patient with multiple system atrophy after three different periods : DIV 1 ( ), DIV 17 ( ), and DIV 50 ( ). – Transgene expression of β-galactosidase (blue) in postmortem tissue from a patient with Parkinson’s disease ( ) and another with AD ( ). The tissue was transfected at DIV 34 and detected at DIV 44 in . In , the tissue was transfected at DIV 14 and the enzyme activity was assessed at DIV 24, and tau pathology was detected using immunocytochemistry (stained with AT8; asterisk, neuritic plaques as black deposits,). – Viability staining of postmortem tissue from an AD patient at DIV 9. Untreated slice. A slice co-cultured with rat embryonic neural stem cells from DIV 0 to DIV 9. Healthy neurons can be surrounded by pathological changes associated with amyloid and neuritic plaques. – Resected brain tissue shows a strong injury response involving reactive cells whose origin is not clearly defined because they can express surprising combinations of markers, like the astrocytic marker GFAP (green) and the microglial marker HLA (red) in tissue from an epilepsy patient at DIV 29 ( ), and like the astrocytic marker S100β (green) and the early neuronal marker TuJ1 (red) in tissue from an epilepsy patient at DIV 26 ( ). , It appeared that the emergence of reactive cells (stained for nestin, a reactive cell marker) was prevented by 24-h treatment of the tissue slices with mitomycin C (a cell-division inhibitor) at DIV 0 (Verwer ., 2015 with permission from Brain Pathology). Untreated slice at DIV 15. Slice treated with mitomycin C at DIV 0 and stained at DIV 15. Symbols in ( – and – ): arrows indicate viable cells, arrowheads denote viable cells with a permeable (leaky) membrane, snake arrows indicate dead cells without esterase enzyme activity and a leaky membrane, asterisks indicate AD pathology, either in the form of plaques (live/dead) or tau pathology. Scale bars: – , , , , and , 100 µm; and , 50 µm; , 25 µm; , 20 µm.