title: Molecular pathways: radiation-induced cognitive impairment.
abstract: Each year, approximately 200,000 patients in the United States will receive partial- or whole-brain irradiation for the treatment of primary or metastatic brain cancer. Early and delayed radiation effects are transient and reversible with modern therapeutic standards; yet, late radiation effects (≥6 months postirradiation) remain a significant risk, resulting in progressive cognitive impairment. These risks include functional deficits in memory, attention, and executive function that severely affect the patient's quality of life. The mechanisms underlying radiation-induced cognitive impairment remain ill defined. Classically, radiation-induced alterations in vascular and neuroinflammatory glial cell clonogenic populations were hypothesized to be responsible for radiation-induced brain injury. Recently, preclinical studies have focused on the hippocampus, one of two sites of adult neurogenesis within the brain, which plays an important role in learning and memory. Radiation ablates hippocampal neurogenesis, alters neuronal function, and induces neuroinflammation. Neuronal stem cells implanted into the hippocampus prevent the decrease in neurogenesis and improve cognition after irradiation. Clinically prescribed drugs, including PPARα and PPARγ agonists, as well as RAS blockers, prevent radiation-induced neuroinflammation and cognitive impairment independent of improved neurogenesis. Translating these exciting findings to the clinic offers the promise of improving the quality of life of brain tumor patients who receive radiotherapy.
authors: Department of Radiation Oncology and Cancer Biology, Wake Forest School of Medicine, Winston-Salem, North Carolina 27157, USA. dgreenes@wakehealth.edu
authors: Dana
authors: D
authors: Greene-Schloesser
authors: Elizabeth
authors: E
authors: Moore
authors: Mike E
authors: ME
authors: Robbins
mesh_terms: D000818:Animals; D001921:Brain / Q000473:pathology / Q000528:radiation effects; D001932:Brain Neoplasms / Q000532:radiotherapy; D003072:Cognition Disorders / Q000209:etiology / Q000473:pathology* / Q000517:prevention & control; D011345:Fenofibrate / Q000494:pharmacology; D006801:Humans; D055495:Neurogenesis / Q000528:radiation effects; D047492:Peroxisome Proliferator-Activated Receptors / Q000819:agonists; D011832:Radiation Injuries / Q000209:etiology / Q000473:pathology* / Q000517:prevention & control; D011833:Radiation Injuries, Experimental / Q000473:pathology; D011837:Radiation-Protective Agents / Q000494:pharmacology; D012084:Renin-Angiotensin System
chemical_list: D047492:Peroxisome Proliferator-Activated Receptors; D011837:Radiation-Protective Agents; D011345:Fenofibrate
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