Figure 5

Systemic chemotherapy leads to increased and prolonged cell death in the adult mouse CNS. Cell death was determined using the terminal deoxynucleotidyltransferase-mediated dUTP nick-end labeling (TUNEL) assay. The number of TUNEL⁺ cells was analyzed in control animals (which received 0.9% NaCl i.p.) and chemotherapy-treated animals and presented as percent normalized values of controls. Each treatment group consisted of n = 5 animals, including control groups at each time point. (a) Animals that received three BCNU (left panel) or cisplatin (right panel) injections (10 mg/kg or 5 mg/kg, respectively, on days 1, 3, and 5) show marked and prolonged increases in cell death in the lateral subventricular zone (SVZ), the corpus callosum (CC) and the dentate gyrus (DG) at 1, 10, and 42 days following treatment (n = 5 animals per group). *P < 0.01. (b) Co-analysis of TUNEL labeling with antigen expression reveals that the great majority of TUNEL⁺ cells in the SVZ and DG are doublecortin⁺ (DCX⁺) neuronal progenitors [44], and that other TUNEL⁺ cells include GFAP⁺ cells (which may be stem cells or astrocytes [45]) and NG2⁺ progenitor cells [46]. In the CC, in contrast, the TUNEL⁺ cells were NG2⁺ glial progenitor cells [47], CNPase⁺ (CNP⁺) oligodendrocytes or GFAP⁺ astrocytes. Co-labeling for TUNEL and myelin basic protein expression revealed results similar to CNPase analysis. Note that close to 100% of TUNEL⁺ cells are accounted for by known lineage markers.