Dexamethasone prevents long-lasting learning impairment following neonatal hypoxic–ischemic brain insult in rats

• Published in: Behavioural brain research Vol. 136; no. 1; pp. 161 - 170
• Main Authors: Ikeda, Tomoaki, Mishima, Kenichi, Yoshikawa, Tetsuya, Iwasaki, Katsunori, Fujiwara, Michihiro, Xia, Yi X., Ikenoue, Tsuyomu
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 17.10.2002
• Subjects: Animals; Animals, Newborn - physiology; Brain - pathology; Choice reaction time task; Conditioning, Operant - drug effects; Dexamethasone; Dexamethasone - pharmacology; Eight-arm radial maze task; Female; Glucocorticoids - pharmacology; Hypoxia-Ischemia, Brain - pathology; Hypoxia-Ischemia, Brain - psychology; Hypoxia–ischemia; Learning Disorders - etiology; Learning Disorders - prevention & control; Learning impairment; Levine's model; Maze Learning - drug effects; Neonatal rat; Pregnancy; Rats; Rats, Wistar; Reaction Time - drug effects; Swimming - psychology; Water maze task; Dexamethasone; Learning impairment; Eight-arm radial maze task; Choice reaction time task; Levine's model; Water maze task; Hypoxia–ischemia; Neonatal rat
• ISSN: 0166-4328; 1872-7549
• DOI: 10.1016/S0166-4328(02)00107-9

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.