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RATIONALE FOR NON-STEROIDAL ANTI-INFLAMMATORY THERAPY
• The radiation-induced blockade of hippocampal neurogenesis is not
attributable to a direct depletion of stem cell populations, but instead of
an inflammatory perturbation of the normal microenvironment that
support neurogenesis
↓
Microglia activation and increase of proinflammatory cytokines
↓
Inhibition of neuronal differentiation of stem cells
• The inflammatory cascade can be mitigated in rodent models by
nonsteroidal anti-inflammatory drugs (pioglitazone, fenofibrate,
angiotensin type 1 receptor antagonists) or other proneurogenic
strategies (aerobic exercise).
Monje et al, Science 2003; Ramanan et al, Int J Radiat Oncol Biol Phys 2009