Dexamethasone prevents long-lasting learning impairment following neonatal hypoxic-ischemic brain insult in rats.
We examined for 18 weeks the effect of dexamethasone treatment on learning and memory impairment produced by hypoxic-ischemic stress at postnatal day 7 in rat in addition to brain histological study. Dexamethasone of 0.5 mg/kg was injected i.p. 4 h before hypoxic-ischemic stress, in which the left carotid artery was ligated followed by 2 h hypoxia (8% oxygen). Dexamethasone treatment improved behavior in each learning task: in choice reaction time tasks relating to the attention process, in 8-arm radial maze task examining working and reference memory, and in water maze task relating to reference memory. Improvement to the extent of the sham-control level was observed. Dexamethasone treatment also completely prevented histological brain damage. No adverse effect in learning and memory tests was observed in the animals treated with dexamethasone without hypoxic-ischemic stress. It is concluded that dexamethasone treatment is significantly effective in prevention not only of histological brain damage but also of learning and memory impairment occasioned by subsequent hypoxic-ischemic insult, warranting further clinical investigation.
Ikeda
Tomoaki
T
Department of Obstetrics and Gynecology, Miyazaki Medical College, 5200 Kihara, Kiyotake-Cho, Japan. tikeda@post1.miyazaki-med.ac.jp
Mishima
Kenichi
K
Yoshikawa
Tetsuya
T
Iwasaki
Katsunori
K
Fujiwara
Michihiro
M
Xia
Yi X
YX
Ikenoue
Tsuyomu
T
D000818:Animals; D000831:Animals, Newborn / Q000502:physiology*; D001921:Brain / Q000473:pathology; D003216:Conditioning, Operant / Q000187:drug effects; D003907:Dexamethasone / Q000494:pharmacology*; D005260:Female; D005938:Glucocorticoids / Q000494:pharmacology*; D020925:Hypoxia-Ischemia, Brain / Q000473:pathology / Q000523:psychology*; D007859:Learning Disabilities / Q000209:etiology / Q000517:prevention & control*; D018782:Maze Learning / Q000187:drug effects; D011247:Pregnancy; D051381:Rats; D017208:Rats, Wistar; D011930:Reaction Time / Q000187:drug effects; D013550:Swimming / Q000523:psychology
D005938:Glucocorticoids; D003907:Dexamethasone