The Conflicting Role of Caffeine Supplementation on Hyperoxia-Induced Injury on the Cerebellar Granular Cell Neurogenesis of Newborn Rats

Figure 10

Schematic illustration of hyperoxia-injured rodent postnatal granular cell neurogenesis with and without caffeine treatment. (a) Hyperoxia reduced granule cell precursors (GPC) and Purkinje cells (PC) in the external granular layer (EGL) and Purkinje cell layer (PCL), respectively (up to P5, dashed red left box). Due to the influence of the high oxygen concentration, the dendrites of the PC were reduced and this resulted in a thinner molecular layer (ML), also after acute hyperoxia. The morphological changes persisted even after recovery in room air until the end of the second week of life (up to P15) and were expressed in reduced PC counts (dashed red right box). Concomitantly, the transcript levels of granular cell-type- and PC cell-specific markers were reduced (see result section). In addition, due to the reduced proliferative capacity after hyperoxia, it seems very likely that essential processes of cerebellar neurogenesis such as migration, proliferation, differentiation, maturation, dendritogenesis, and synaptogenesis are damaged by the early oxygen insult (red dashed lines, inhibition). Caffeine (dashed green left and right boxes) was able to reduce the effects of oxidative stress with respect to PCs, GPCs, and mitotic stages of GCs (green and blue lines, activation) but otherwise showed poor protective effects on granular cell neurogenesis (see Results). (b) Cellular players in cerebellar granular cell neurogenesis.