17beta-estradiol and enriched environment accelerate cognitive recovery after focal brain ischemia
2009 (English)In: European Journal of Neuroscience, ISSN 0953-816X, E-ISSN 1460-9568, Vol. 29, no 6, 1215-1224 p.Article in journal (Refereed) Published
Cognitive impairments, including spatial memory and learning deficiencies, are common after ischemic stroke. Estrogen substitution improves cognitive functions in post-menopausal women and ovariectomized rodents, partially through induction of neuroplasticity in the hippocampal formation. Post-ischemic housing of male rats in an enriched environment (EE) improves functional outcome, without changing infarct volume. We hypothesized that 17beta-estradiol combined with an EE would accelerate cognitive recovery after focal brain ischemia in ovariectomized rats and that recovery would be related to altered expression of nerve growth factor-induced gene (NGFI)-A in the hippocampus. 17beta-estradiol or placebo pellets were implanted 6 h after transient middle cerebral artery occlusion. Two days later, rats were placed in an EE or a deprived environment (DE) for 6 weeks. At 5 weeks after middle cerebral artery occlusion, 17beta-estradiol-treated rats housed in an EE showed improvements in cognitive function (i.e. shorter latency and path in the Morris water maze task) compared with placebo-treated animals housed in an EE. Furthermore, beneficial effects on latency and path were observed when comparing EE-housed vs. DE-housed 17beta-estradiol-treated rats. When comparing 17beta-estradiol-treated EE-housed rats vs. placebo-treated DE-housed rats, pronounced effects on latency and path were observed. Infarct volumes did not differ between groups. 17beta-estradiol-treated EE-housed rats had significantly higher NGFI-A mRNA expression bilaterally in the cornu ammonis 1 region and in the ipsilateral dentate gyrus of the hippocampus, compared with placebo-treated EE-housed rats. In conclusion, 17beta-estradiol treatment combined with an EE improved recovery of cognitive function after experimental brain ischemia, putatively through the upregulation of NGFI-A in hippocampal subregions.
Place, publisher, year, edition, pages
Hoboken: Wiley-Blackwell, 2009. Vol. 29, no 6, 1215-1224 p.
environmental enrichment, estrogen, hippocampus, ischemic stroke, learning and memory, rat
IdentifiersURN: urn:nbn:se:umu:diva-32402DOI: 10.1111/j.1460-9568.2009.06662.xISI: 000264065500012PubMedID: 19302156OAI: oai:DiVA.org:umu-32402DiVA: diva2:303090