RESUMO
It has been elucidated that cognitive dysfunction following cranial radiotherapy might be linked to the oxidative stress-induced impairment of hippocampal neurogenesis that is mediated by proliferating neural stem or progenitor cells. The novel free-radical scavenger edaravone (3-methyl-1-phenyl-2-pyrazolin-5-one) has been clinically used to reduce neuronal damage following ischemic stroke. Previously, we reported that the free-radical scavenger, edaravone, which is currently used to treat patients with brain ischemia, protected cultured human neural stem cells (NSCs) from radiation-induced cell death; the protective effect was observed more significantly in NSCs than in brain tumor cells. Here, in animal models, we demonstrate that edaravone protects neurons in the subgranular zone (SGZ) of the dentate gyrus of the hippocampus from cell death after irradiation. Moreover, edaravone protected spatial memory retention deficits as determined by Morris water maze tests. Our study may shed some light on the beneficial effects of free-radical scavengers in impaired neurogenesis following cranial radiation therapy.
Assuntos
Antipirina/análogos & derivados , Giro Denteado/efeitos dos fármacos , Sequestradores de Radicais Livres/farmacologia , Aprendizagem em Labirinto/efeitos dos fármacos , Células-Tronco Neurais/efeitos dos fármacos , Animais , Antipirina/farmacologia , Antipirina/uso terapêutico , Apoptose/efeitos dos fármacos , Apoptose/efeitos da radiação , Células Cultivadas , Giro Denteado/patologia , Giro Denteado/efeitos da radiação , Edaravone , Sequestradores de Radicais Livres/uso terapêutico , Masculino , Aprendizagem em Labirinto/efeitos da radiação , Camundongos , Camundongos Endogâmicos C57BL , Células-Tronco Neurais/patologia , Células-Tronco Neurais/efeitos da radiação , Neurogênese/efeitos dos fármacos , Neurogênese/efeitos da radiação , Lesões Experimentais por Radiação/patologia , Lesões Experimentais por Radiação/prevenção & controleRESUMO
The response of cancer patients to interferon (IFN) treatment is long-lasting, indicating that IFN may act on small cancer stem cell populations. Glioma-initiating cells (GICs) can self-renew and induce the formation of heterogeneously differentiated tumor cells and are resistant to chemotherapeutic agents like temozolomide. In this study, we showed that via STAT3 signaling, IFN-beta suppressed the proliferation, self-renewal, and tumorigenesis of GICs, induced their terminal differentiation to mature oligodendroglia-like cells, and exhibited synergistic cytotoxicity with temozolomide. Therefore, IFN may be a potential therapeutic agent for inducing the terminal differentiation of GICs.