Neurovascular coupling alterations in vivo caused by irradiation in mice

NAISS 2023/6-362


NAISS Medium Storage

Principal Investigator:

Klas Blomgren


Karolinska Institutet

Start Date:


End Date:


Primary Classification:

30105: Neurosciences

Secondary Classification:

30203: Cancer and Oncology



The neurovascular unit (NVU) is the core component of the blood-brain barrier, responsible for NVC), which fine-tunes blood flow to meet the high metabolic demand of the brain. Although the precise cellular mechanisms are largely unknown, our experimental data suggest that NVC impairment precedes physical hallmarks and cognitive decline in normal brain aging and accelerated aging triggered by for example radiation. Cancer patients subjected to cranial radiotherapy display a higher incidence of cerebrovascular disorders, at earlier ages, and their brains are known to degenerate at a faster rate, parallel to cognitive decline. Brain irradiation (IR), e.g. in cancer treatment, causes complex brain damage, particularly in juvenile, still developing, brains. IR accelerates brain degeneration and dramatically increases the risk for cerebrovascular disease. In rodents, brain IR mimics features of premature brain aging, including long-term neuroinflammation. Our ultimate goal is to prevent - or even reverse - brain aging. Our hypothesis is that restoration of NVC function is sufficient to reach this goal. With this purpose, one of our first aims is to analyze NVC pathways affected by IR by performing single-cell RNA-sequence in relevant brain regions at time points 6h, 1 day, 7 days, 6 weeks, 11 weeks, 6 months and 1 year after IR in juvenile mice. This will enable us to identify which cells that are affected by IR, and when. This will generate a transcriptomic map of the cellular events leading up to NVC loss after IR. 1 Roddy, E. & Mueller, S. Late Effects of Treatment of Pediatric Central Nervous System Tumors. J Child Neurol 31, 237-254, doi:10.1177/0883073815587944 (2016). 2 Monje, M. L., Mizumatsu, S., Fike, J. R. & Palmer, T. D. Irradiation induces neural precursor cell dysfunction. Nat Med 8, 955-962 (2002).