A free-radical scavenger protects the neural progenitor cells in the dentate subgranular zone of the hippocampus from cell death after X-irradiation.
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.
Motomura
Kazuya
K
Department of Neurosurgery, Nagoya University School of Medicine, Japan.
Ogura
Masatoshi
M
Natsume
Atsushi
A
Yokoyama
Hidenori
H
Wakabayashi
Toshihiko
T
D000818:Animals; D000983:Antipyrine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects; D002478:Cells, Cultured; D018891:Dentate Gyrus / Q000187:drug effects* / Q000473:pathology / Q000528:radiation effects; D000077553:Edaravone; D016166:Free Radical Scavengers / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D018782:Maze Learning / Q000187:drug effects* / Q000528:radiation effects; D051379:Mice; D008810:Mice, Inbred C57BL; D058953:Neural Stem Cells / Q000187:drug effects* / Q000473:pathology / Q000528:radiation effects; D055495:Neurogenesis / Q000187:drug effects / Q000528:radiation effects; D011833:Radiation Injuries, Experimental / Q000473:pathology / Q000517:prevention & control
D016166:Free Radical Scavengers; D000077553:Edaravone; D000983:Antipyrine