Radiation research
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Cognitive impairment precipitated by irradiation of normal brain tissue is commonly associated with radiation therapy for treatment of brain cancer, and typically manifests more than 6 months after radiation exposure. The risks of cognitive impairment are of particular concern for an increasing number of long-term cancer survivors. There is presently no effective means of preventing or mitigating this debilitating condition. ⋯ Cell proliferation and neurogenesis in the dentate gyrus were assayed at 2 months post-WBI, whereas novel object recognition and long-term potentiation were assayed at 6 and 9 months post-WBI, respectively. MW-151 mitigated radiation-induced neuroinflammation at both early and late time points post-WBI, selectively mitigated the deleterious effects of irradiation on hippocampal neurogenesis, and potently mitigated radiation-induced deficits of novel object recognition consolidation and of long-term potentiation induction and maintenance. Our results suggest that transient administration of MW-151 is sufficient to partially preserve/restore neurogenesis within the subgranular zone and to maintain the functional integrity of the dentate gyrus long after MW-151 therapy withdrawal.