Combination treatment of neonatal rats with hypoxia-ischemia and endotoxin induces long-lasting memory and learning impairment that is associated with extended cerebral damage

Autor: Tomoaki Ikeda, Kenichi Mishima, Tsuyomu Ikenoue, Naoya Aoo, Nobuaki Egashira, Michihiro Fujiwara, Katsunori Iwasaki
Rok vydání: 2004
Předmět:
Zdroj: American Journal of Obstetrics and Gynecology. 191:2132-2141
ISSN: 0002-9378
DOI: 10.1016/j.ajog.2004.04.039
Popis: Objective We assessed the long-term effects of perinatal hypoxia-ischemia and endotoxin on attention and short- and long-term memory in neonatal rats with the use of behavioral tasks and brain histologic results. Study design Four hours after injections of lipopolysaccharide (1 mg/kg, intraperitoneally) or saline solution, 7-day-old Wistar rat pups were subjected to unilateral hypoxia-ischemia for 1 hour. We studied 4 groups: controls (n = 43 rats), lipopolysaccharide alone (n = 12 rats), hypoxia-ischemia alone (n = 29 rats), and combined lipopolysaccharide + hypoxia-ischemia treatment (n = 34 rats). Seven to 16 weeks after the treatment, we measured attention with a choice reaction time task, short-term memory with an 8-arm radial maze task, and long-term memory with a water maze task. At 19 weeks of age, the brain was removed, fixed, and sectioned coronally; and the volume of each part was measured. Results A loss of volume in the hippocampus was observed in the lipopolysaccharide, hypoxia-ischemia, and lipopolysaccharide + hypoxia-ischemia groups; a loss of striatum was observed in the hypoxia-ischemia and lipopolysaccharide + hypoxia-ischemia groups, but loss of cortex was observed only in the lipopolysaccharide + hypoxia-ischemia group. The lipopolysaccharide, hypoxia-ischemia, and lipopolysaccharide + hypoxia-ischemia groups showed significantly poorer performance (attention deficit) than controls in the choice reaction time task. Correct choices decreased, and error increased in the lipopolysaccharide + hypoxia-ischemia group compared with the other groups in the radial maze task, which shows short-term memory impairment. Swimming distance was significantly greater in the hypoxia-ischemia and lipopolysaccharide + hypoxia-ischemia groups than in the other 2 groups in the water maze test, which shows long-term memory impairment. Conclusion Combined lipopolysaccharide and hypoxia-ischemia treatment synergistically induced short-term memory impairment that is associated with loss of cortical volume.
Databáze: OpenAIRE
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