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• W3096021787 endingPage "147196" @default.
• W3096021787 startingPage "147196" @default.
• W3096021787 abstract "Acute ischemic stroke (AIS) causes both central and peripheral inflammation, while activation of α7 nicotinic acetylcholine receptors (nAChRs) provides both central and peripheral anti-inflammatory and anti-apoptotic effects. Here, we provide evidence that 4OH-GTS-21, a selective α7 agonist, produces its therapeutic effects via primarily central sites of action because 4OH-GTS-21 was found equally effective in splenectomized and non-spenectomized rats in the sub-acute phase of ischemic stroke (≤1 week). However, the spleen may boost the therapeutic efficacy of 4OH-GTS-21 in certain behavioral tasks as our data also indicated. In our tests, AIS was modeled by transient middle cerebral artery occlusion (tMCAO). Splenectomy was done 2 weeks before tMCAO. We determined that: 1) Daily 4OH-GTS-21 treatments for 7 days after tMCAO significantly reduced neurological deficits and brain injury in both splenectomized and non-spelenectomized rats demonstrating that the spleen is not required for therapeutic benefits of 4OH-GTS-21; 2) The effects of 4OH-GTS-21 in the adhesive sticker removal test were significantly weaker in splenectomized animals suggesting that the spleen boosts the efficacy of 4OH-GTS-21 in the first week after tMCAO; and 3) Ischemic brain injury was not significantly affected by splenectomy in both vehicle-treated and 4OH-GTS-21-treated animals. These data support the hypothesis that the therapeutic efficacy of sub-chronic (≤1 week) 4OH-GTS-21 primarily originates from central sites of action. These results validate brain availability as a critical factor for developing novel α7 ligands for AIS." @default.
• W3096021787 created "2020-11-09" @default.
• W3096021787 creator A5023563705 @default.
• W3096021787 creator A5071834862 @default.
• W3096021787 creator A5083561854 @default.
• W3096021787 date "2021-01-01" @default.
• W3096021787 modified "2023-09-25" @default.
• W3096021787 title "Spleen is not required for therapeutic effects of 4OH-GTS-21, a selective α7 nAChR agonist, in the sub-acute phase of ischemic stroke in rats" @default.
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• W3096021787 doi "https://doi.org/10.1016/j.brainres.2020.147196" @default.
• W3096021787 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/33159972" @default.
• W3096021787 hasPublicationYear "2021" @default.
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