Abstract
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% N2 at 33°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.
Similar content being viewed by others
Log in or create a free account to read this content
Gain free access to this article, as well as selected content from this journal and more on nature.com
or
Abbreviations
- CRT:
-
choice reaction time
- HI:
-
Hypoxia-ischemia, or hypoxic-ischemic
References
Rice JE 3rd, Vannucci RC, Brierley JB 1981 The influence of immaturity on hypoxic-ischemic brain damage in the rat. Ann Neurol 9: 131–141
Ikeda T, Mishima K, Yoshikawa T, Iwasaki K, Fujiwara M, Xia YX, Ikenoue T 2001 Selective and long-term learning impairment following neonatal hypoxic-ischemic brain insult in rats. Behav Brain Res 118: 17–25
Arteni NS, Salgueiro J, Torres I, Achaval M, Netto CA 2003 Neonatal cerebral hypoxia-ischemia causes lateralized memory impairments in the adult rat. Brain Res 973: 171–178
Hagberg H, Bona E, Gilland E, Puka-Sundvall M 1997 Hypoxia-ischaemia model in the 7-day-old rat: possibilities and shortcomings. Acta Paediatr Suppl 422: 85–88
Mishima K, Ikeda T, Aoo N, Takai N, Takahashi S, Egashira N, Ikenoue T, Iwasaki K, Fujiwara M 2005 Hypoxia-ischemic insult in neonatal rats induced slowly progressive brain damage related to memory impairment. Neurosci Lett 376: 194–199
Levine S, Haltmeyer GC, Karas GG, Denenberg VH 1967 Physiological and behavioral effects of infantile stimulation. Physiol Behav 2: 55–59
Chou IC, Trakht T, Signori C, Smith J, Felt BT, Vazquez DM, Barks JD 2001 Behavioral/environmental intervention improves learning after cerebral hypoxia-ischemia in rats. Stroke 32: 2192–2197
Dahlqvist P, Ronnback A, Bergstrom SA, Soderstrom I, Olsson T 2004 Environmental enrichment reverses learning impairment in the Morris water maze after focal cerebral ischemia in rats. Eur J Neurosci 19: 2288–2298
Fernandez-Teruel A, Gimenez-Llort L, Escorihuela RM, Gil L, Aguilar R, Steimer T, Tobena A 2002 Early-life handling stimulation and environmental enrichment: are some of their effects mediated by similar neural mechanisms?. Pharmacol Biochem Behav 73: 233–245
Biernaskie J, Corbett D 2001 Enriched rehabilitative training promotes improved forelimb motor function and enhanced dendritic growth after focal ischemic injury. J Neurosci 21: 5272–5280
Mortola JP, Dotta A 1992 Effects of hypoxia and ambient temperature on gaseous metabolism of newborn rats. Am J Physiol 263: R267–R272
Morris RG 1981 Spatial localization dose not require the presence of local cues. Learn Motiv 12: 239–260
Marin R, Williams A, Hale S, Burge B, Mense M, Bauman R, Tortella F 2003 The effect of voluntary exercise exposure on histological and neurobehavioral outcomes after ischemic brain injury in the rat. Physiol Behav 80: 167–175
Dahlqvist P, Zhao L, Johansson IM, Mattsson B, Johansson BB, Seckl JR, Olsson T 1999 Environmental enrichment alters nerve growth factor-induced gene A and glucocorticoid receptor messenger RNA expression after middle cerebral artery occlusion in rats. Neuroscience 93: 527–535
Rowntree S, Kolb B 1997 Blockade of basic fibroblast growth factor retards recovery from motor cortex injury in rats. Eur J Neurosci 9: 2432–2441
Wilson DA, Willner J, Kurz EM, Nadel L 1986 Early handling increases hippocampal long-term potentiation in young rats. Behav Brain Res 21: 223–227
van Praag H, Kempermann G, Gage FH 1999 Running increases cell proliferation and neurogenesis in the adult mouse dentate gyrus. Nat Neurosci 2: 266–270
Faverjon S, Silveira DC, Fu DD, Cha BH, Akman C, Hu Y, Holmes GL 2002 Beneficial effects of enriched environment following status epilepticus in immature rats. Neurology 59: 1356–1364
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Ikeda, T., Mishima, K., Aoo, N. et al. Rehabilitative Training Tasks Improve Spatial Learning Impairment in the Water Maze Following Hypoxic-Ischemic Insult in Neonatal Rats. Pediatr Res 59, 61–65 (2006). https://doi.org/10.1203/01.pdr.0000190582.49589.14
Received:
Accepted:
Issue date:
DOI: https://doi.org/10.1203/01.pdr.0000190582.49589.14
This article is cited by
-
Differential Progression of Magnetization Transfer Imaging Changes Depending on Severity of Cerebral Hypoxic-Ischemic Injury
Journal of Cerebral Blood Flow & Metabolism (2008)
-
ROCK inhibition produces anxiety-related behaviors in mice
Psychopharmacology (2006)


