Radiation Induced Cognitive Decline - Alterations in Hippocampus Microenvironment

Alterations in Hippocampus Microenvironment

The microenvironment is an important component to consider for precursor survival and differentiation. It is the microenvironment that provides the signals to the precursor cells that help it survive, proliferate, and differentiate. To determine if the microenvironment is altered as a result of radiation, an animal study was performed by Fike et al. where highly enriched, BrdU labeled, non-irradiated stem cells from a rat hippocampus were implanted into a hippocampus that was irradiated one month prior. The stem cells were allowed to remain in the live rat for 3–4 weeks. Afterwards, the rat was killed and the stem cells were observed using immunohistochemistry and confocal microscopy. The results show that stem cell survival was similar to that found in a control subject (normal rat hippocampus); however, the number of neurons generated was decreased by 81%. Therefore, alterations of the microenvironment post radiation can lead to a decrease in neurogenesis.

In addition, studies mentioned by Fike et al. found that there are two main differences between the hippocampus of an irradiated rat and a non-irradiated rat that are part of the microenvironment. There was a significantly larger number of activated microglia cells in the hippocampus of irradiated rats in comparison to non-irradiated rats. The presence of microglia cells is characteristic of the inflammatory response which is most likely due to radiation exposure. Also the expected clustering of stem cells around the vasculature of the hippocampus was disrupted. Therefore focusing on the microglial activation, inflammatory response, and microvasculature may produce a direct link to the decrease in neurogenesis post irradiation.