Bcl2 ‐Expressing Quiescent Type B Neural Stem Cells in the Ventricular–Subventricular Zone Are Resistant to Concurrent Temozolomide/X‐Irradiation

The brain's ventricular –subventricular zone is a site of type B neural stem cell‐mediated neurogenesis and unfortunately for very aggressive glioblastoma. Treatment for glioblastoma consists of resection, concurrent temozolomide, and X‐irradiation, followed by adjuvant temozolomide. We show that concurrent temozolom ide/X‐irradiation followed by adjuvant temozolomide induces apoptosis in type A neuroblasts. In contrast, quiescent neural stem cells, which express high levels of Bcl2 and Mcl1, survive and repopulate type A neuroblasts. AbstractThe ventricular –subventricular zone (V‐SVZ) of the mammalian brain is a site of adult neurogenesis. Within the V‐SVZ reside type B neural stem cells (NSCs) and type A neuroblasts. The V‐SVZ is also a primary site for very aggressive glioblastoma (GBM). Standard‐of‐care therapy for GBM consists of safe maximum resection, concurrent temozolomide (TMZ), and X‐irradiation (XRT), followed by adjuvant TMZ therapy. The question of how this therapy impacts neurogenesis is not well understood and is of fundamental importance as normal tissue tolerance is a limiting factor. Here, we studied the effects o f concurrent TMZ/XRT followed by adjuvant TMZ on type B stem cells and type A neuroblasts of the V‐SVZ in C57BL/6 mice. We found that chemoradiation induced an apoptotic response in type A neuroblasts, as marked by cleavage of Caspase‐3, but not in NSCs, and that A cells within the V‐SVZ were repopulated given ...
Source: Stem Cells - Category: Stem Cells Authors: Tags: Translational and Clinical Research Source Type: research

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Source: Stem Cells - Category: Stem Cells Authors: Tags: Tissue ‐Specific Stem Cells Source Type: research
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