title: Insulin-Like Growth Factor (IGF)-I Modulates Endothelial Blood-Brain Barrier Function in Ischemic Middle-Aged Female Rats.
abstract: In comparison with young females, middle-aged female rats sustain greater cerebral infarction and worse functional recovery after stroke. These poorer stroke outcomes in middle-aged females are associated with an age-related reduction in IGF-I levels. Poststroke IGF-I treatment decreases infarct volume in older females and lowers the expression of cytokines in the ischemic hemisphere. IGF-I also reduces transfer of Evans blue dye to the brain, suggesting that this peptide may also promote blood-brain barrier function. To test the hypothesis that IGF-I may act at the blood-brain barrier in ischemic stroke, 2 approaches were used. In the first approach, middle-aged female rats were subjected to middle cerebral artery occlusion and treated with IGF-I after reperfusion. Mononuclear cells from the ischemic hemisphere were stained for CD4 or triple-labeled for CD4/CD25/FoxP3 and subjected to flow analyses. Both cohorts of cells were significantly reduced in IGF-I-treated animals compared with those in vehicle controls. Reduced trafficking of immune cells to the ischemic site suggests that blood-brain barrier integrity is better maintained in IGF-I-treated animals. The second approach directly tested the effect of IGF-I on barrier function of aging endothelial cells. Accordingly, brain microvascular endothelial cells from middle-aged female rats were cultured ex vivo and subjected to ischemic conditions (oxygen-glucose deprivation). IGF-I treatment significantly reduced the transfer of fluorescently labeled BSA across the endothelial monolayer as well as cellular internalization of fluorescein isothiocyanate-BSA compared with those in vehicle-treated cultures, Collectively, these data support the hypothesis that IGF-I improves blood-brain barrier function in middle-aged females.
authors.affiliation: Women's Health in Neuroscience Program (S.B., A.K.O., F.S.), Department of Neuroscience and Experimental Therapeutics and Department of Microbial Pathogenesis and Immunology (R.C.A.), Texas A&M University Health Science Center, Bryan, Texas 77807.
authors.forename: Shameena
authors.initials: S
authors.lastname: Bake
authors.affiliation: Women's Health in Neuroscience Program (S.B., A.K.O., F.S.), Department of Neuroscience and Experimental Therapeutics and Department of Microbial Pathogenesis and Immunology (R.C.A.), Texas A&M University Health Science Center, Bryan, Texas 77807.
authors.forename: Andre K
authors.initials: AK
authors.lastname: Okoreeh
authors.affiliation: Women's Health in Neuroscience Program (S.B., A.K.O., F.S.), Department of Neuroscience and Experimental Therapeutics and Department of Microbial Pathogenesis and Immunology (R.C.A.), Texas A&M University Health Science Center, Bryan, Texas 77807.
authors.forename: Robert C
authors.initials: RC
authors.lastname: Alaniz
authors.affiliation: Women's Health in Neuroscience Program (S.B., A.K.O., F.S.), Department of Neuroscience and Experimental Therapeutics and Department of Microbial Pathogenesis and Immunology (R.C.A.), Texas A&M University Health Science Center, Bryan, Texas 77807.
authors.forename: Farida
authors.initials: F
authors.lastname: Sohrabji
mesh_terms: D000375:Aging; D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D002545:Brain Ischemia / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D002199:Capillary Permeability / Q000187:drug effects; D015687:Cell Hypoxia / Q000187:drug effects; D002478:Cells, Cultured; D054022:Cerebrum / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D004343:Drug Implants; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D007003:Hypoglycemia / Q000209:etiology; D007334:Insulin-Like Growth Factor I / Q000008:administration & dosage / Q000235:genetics / Q000494:pharmacology / Q000627:therapeutic use*; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D055806:Microvessels / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D009419:Nerve Tissue Proteins / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D017526:Receptor, IGF Type 1 / Q000819:agonists* / Q000378:metabolism; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D015398:Signal Transduction / Q000187:drug effects*; D020521:Stroke / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism / Q000473:pathology
chemical_list: D004343:Drug Implants; C583557:IGF1 protein, human; D009419:Nerve Tissue Proteins; D011994:Recombinant Proteins; D007334:Insulin-Like Growth Factor I; D017526:Receptor, IGF Type 1