The hippocampal neurovascular niche during normal development and after irradiation to the juvenile mouse brain

Abstract

Purpose: To investigate the effects of cranial irradiation on the neurovascular niche in the young brain. Disruption of this niche has previously been observed in the adult rat brain after irradiation.

Materials and methods: We subjected postnatal day 14 (P14) mice to a single dose of 8 Gy whole brain irradiation and measured the distance between microvessels and either neural progenitor cells (doublecortin-positive, DCX(+)) or proliferating cells (Ki-67(+)) in the dorsal hippocampal subgranular zone (SGZ) 6 hours, 1 week and 7 weeks post-irradiation. In addition, pericyte coverage of microvessels in the SGZ was measured.

Results: DCX(+) and Ki-67(+) cells were located closer to microvessels in the adult brain compared to young, still growing brains, constituting new information on normal development. We found an increased distance between microvessels and DCX(+) cells 6 h post-irradiation and between microvessels and Ki-67(+) cells 1 week post-irradiation. Furthermore, pericyte coverage was transiently decreased by 17% 6 h post-irradiation.

Conclusions: The hippocampal neurovascular niche in the young, growing brain is transiently disrupted by irradiation. It remains to be elucidated what role these transient changes play in the apparently permanent ablation of hippocampal neurogenesis previously demonstrated in the same model.

Keywords: Brain development; endothelium; neurogenesis; neurovascular unit; pericyte; radiation therapy.