Enhanced lithium-induced brain recovery following cranial irradiation is not impeded by inflammation.

Journal Article (Journal Article)

Radiation-induced brain injury occurs in many patients receiving cranial radiation therapy, and these deleterious effects are most profound in younger patients. Impaired neurocognitive functions in both humans and rodents are associated with inflammation, demyelination, and neural stem cell dysfunction. Here we evaluated the utility of lithium and a synthetic retinoid receptor agonist in reducing damage in a model of brain-focused irradiation in juvenile mice. We found that lithium stimulated brain progenitor cell proliferation and differentiation following cranial irradiation while also preventing oligodendrocyte loss in the dentate gyrus of juvenile mice. In response to inflammation induced by radiation, which may have encumbered the optimal reparative action of lithium, we used the anti-inflammatory synthetic retinoid Am80 that is in clinical use in the treatment of acute promyelocytic leukemia. Although Am80 reduced the number of cyclooxygenase-2-positive microglial cells following radiation treatment, it did not enhance lithium-induced neurogenesis recovery, and this alone was not significantly different from the effect of lithium on this proinflammatory response. Similarly, lithium was superior to Am80 in supporting the restoration of new doublecortin-positive neurons following irradiation. These data suggest that lithium is superior in its restorative effects to blocking inflammation alone, at least in the case of Am80. Because lithium has been in routine clinical practice for 60 years, these preclinical studies indicate that this drug might be beneficial in reducing post-therapy late effects in patients receiving cranial radiotherapy and that blocking inflammation in this context may not be as advantageous as previously suggested.

Full Text

Duke Authors

Cited Authors

  • Malaterre, J; McPherson, CS; Denoyer, D; Lai, E; Hagekyriakou, J; Lightowler, S; Shudo, K; Ernst, M; Ashley, DM; Short, JL; Wheeler, G; Ramsay, RG

Published Date

  • June 2012

Published In

Volume / Issue

  • 1 / 6

Start / End Page

  • 469 - 479

PubMed ID

  • 23197851

Pubmed Central ID

  • PMC3659714

International Standard Serial Number (ISSN)

  • 2157-6564

Digital Object Identifier (DOI)

  • 10.5966/sctm.2011-0046


  • eng

Conference Location

  • England