Radiation-induced brain injury (RIBI) after radiotherapy has become an increasingly important factor affecting the prognosis of patients with head and neck tumor. With the delivery of high doses of radiation to brain tissue, microglia rapidly transit to a pro-inflammatory phenotype, upregulate phagocytic machinery, and reduce the release of neurotrophic factors. Persistently activated microglia mediate the progression of chronic neuroinflammation, which may inhibit brain neurogenesis leading to the occurrence of neurocognitive disorders at the advanced stage of RIBI. Fully understanding the microglial pathophysiology and cellular and molecular mechanisms after irradiation may facilitate the development of novel therapy by targeting microglia to prevent RIBI and subsequent neurological and neuropsychiatric disorders.

Epimedium brevicornum Maxim, a Traditional Chinese Medicine, has been used for the treatment of impotence, sinew and bone disorders, "painful impediment caused by wind-dampness," numbness, spasms, hypertension, coronary heart disease, menopausal syndrome, bronchitis, and neurasthenia for many years in China. Recent animal experimental studies indicate that icariin, a major bioactive component of epimedium may effectively treat Alzheimer's disease, cerebral ischemia, depression, Parkinson's disease, multiple sclerosis, as well as delay ageing. Our recent study also suggested that epimedium extract could exhibit radio-neuroprotective effects and prevent ionizing radiation-induced impairment of neurogenesis. This paper reviewed the pharmacodynamics of icariin in treating different neurodegenerative and neuropsychiatric diseases, ageing, and radiation-induced brain damage. The relevant molecular mechanisms and its anti-neuroinflammatory, antiapoptotic, anti-oxidant, as well as pro-neurogenesis roles were also discussed.

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