title: 17beta-estradiol and enriched environment accelerate cognitive recovery after focal brain ischemia.
abstract: 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.
authors.affiliation: Department of Public Health and Clinical Medicine, Medicine, Umeå University, Umeå, Sweden. ingegerd.soderstrom@medicin.umu.se
authors.forename: Ingegerd
authors.initials: I
authors.lastname: Söderström
authors.forename: Magnus
authors.initials: M
authors.lastname: Strand
authors.forename: Anna-Cajsa
authors.initials: AC
authors.lastname: Ingridsson
authors.forename: Salmir
authors.initials: S
authors.lastname: Nasic
authors.forename: Tommy
authors.initials: T
authors.lastname: Olsson
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D020520:Brain Infarction / Q000188:drug therapy / Q000209:etiology; D002545:Brain Ischemia / Q000150:complications; D003072:Cognition Disorders / Q000188:drug therapy* / Q000209:etiology / Q000451:nursing* / Q000473:pathology; D004195:Disease Models, Animal; D051766:Early Growth Response Protein 1 / Q000235:genetics / Q000378:metabolism; D004777:Environment; D004958:Estradiol / Q000097:blood / Q000627:therapeutic use*; D004967:Estrogens / Q000097:blood / Q000627:therapeutic use*; D005260:Female; D007839:Functional Laterality / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects; D009043:Motor Activity / Q000187:drug effects; D009483:Neuropsychological Tests; D010052:Ovariectomy / Q000379:methods; D011597:Psychomotor Performance / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000187:drug effects; D020127:Recovery of Function / Q000187:drug effects* / Q000502:physiology; D012677:Sensation / Q000187:drug effects; D013997:Time Factors; D014738:Vibrissae / Q000187:drug effects / Q000294:innervation
chemical_list: D051766:Early Growth Response Protein 1; C486110:Egr1 protein, rat; D004967:Estrogens; D004958:Estradiol