Depletion of Neural Precursor Cells after Local Brain Irradiation is due to Radiation Dose to the Parenchyma, not the Vasculature

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Abstract
The underlying mechanisms associated with radiation-induced cognitive impairments remain elusive but may involve changes in hippocampal neural precursor cells. Proliferating neural precursor cells have been shown to be extremely sensitive to X rays, either from damage to the cells themselves and/or through microenvironmental factors, including the anatomical relationship with the microvasculature, which is altered by radiation. The neutron capture reaction in boron was used to determine whether the sensitivity of neural precursor cells was dominated by direct radiation effects or was mediated through changes in the microvasculature. Young adult rats were irradiated with X rays, neutrons only, or neutrons plus either mercapto-undecahydro-dodecaborane (BSH) or p-dihydroxyboryl-phenylalanine (BPA). BSH remains inside cerebral vessels, thereby limiting the neutron capture intravascularly; BPA readily passes into the parenchyma. One month after irradiation, cell proliferation and numbers of immature neurons were determined using immunohistochemistry. Results showed that (1) neural precursor cells and their progeny were decreased in a dose-dependent manner by mixed high- and low-LET radiation, and (2) selective irradiation of the microvasculature resulted in less loss of neural precursor cells than when the radiation dose was delivered uniformly to the parenchyma. This information, and in particular the approach of selectively irradiating the vasculature, may be useful in developing radioprotective compounds for use during therapeutic irradiation.