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We recently reported that hypoxic-ischemic (HI) insult to the brain of 7-d-old rats resulted in a slowly progressive learning and memory disability, which started at around 5 wk after HI, a time frame that is representative of human adolescence. The purpose of the present study was to examine whether physical or mental exercises can prevent this late-onset, slowly progressing disability. Wistar rats were subjected to left carotid ligation followed by 2 h of hypoxic stress (8% O2 and 92% N(2) at 33 degrees C). Sham-control rats were subjected to the same procedure without ligation and hypoxic stress. Six weeks after the HI, the animals were divided into four groups: pretraining control, no training control, pretraining HI, and no training HI groups. We used the plus maze, eight-arm radial maze, and choice reaction time task as the rehabilitative training. Sixteen weeks after the HI, the water maze task was performed over 5 d to evaluate spatial learning ability; thereafter, cerebral morphology of the animals was examined. There were no differences in swimming length and latency between the pretraining control and no training control groups. Swimming length and latency in the pretraining HI group were significantly shorter and swifter than those in the no training HI group. The infarct areas on the left cerebral hemisphere were equivalent between pretraining HI and no training HI groups at each sectional slice. Rehabilitative training tasks prevented the neonatal HI-induced late-onset slowly progressive learning and memory disability.

Rehabilitative Training Tasks Improve Spatial Learning Impairment in the Water Maze Following Hypoxic-Ischemic Insult in Neonatal Rats