Author(s): Jing Chen-Roetling and Raymond F. Regan*
Page: [2226 - 2237] Pages: 12
* (Excluding Mailing and Handling)
Background: Injury to cells adjacent to an intracerebral hemorrhage (ICH) is likely mediated at least in part by toxins released from the hematoma that initiate complex and interacting injury cascades. Pharmacotherapies targeting a single toxin or pathway, even if consistently effective in controlled experimental models, have a high likelihood of failure in a variable clinical setting. Nuclear factor erythroid-2 related factor 2 (Nrf2) regulates the expression of heme oxygenase-1 (HO-1) and multiple other proteins with antioxidant and antiinflammatory effects, and may be a target of interest after ICH.
Methods: Studies that tested the effect of HO and Nrf2 in models relevant to ICH are summarized, with an effort to reconcile conflicting data by consideration of methodological limitations. Results: In vitro studies demonstrated that Nrf2 activators rapidly increased HO-1 expression in astrocytes, and reduced their vulnerability to hemoglobin or hemin. Modulating HO-1 expression via genetic approaches yielded similar results. Systemic treatment with small molecule Nrf2 activators increased HO-1 expression in perivascular cells, particularly astrocytes. When tested in mouse or rat ICH models, Nrf2 activators were consistently protective, improving barrier function and attenuating edema, inflammation, neuronal loss and neurological deficits. These effects were mimicked by selective astrocyte HO-1 overexpression in transgenic mice. Conclusion: Systemic treatment with Nrf2 activators after ICH is protective in rodents. Two compounds, dimethyl fumarate and hemin, are currently approved for treatment of multiple sclerosis and acute porphyria, respectively, and have acceptable safety profiles over years of clinical use. Further development of these drugs as ICH therapeutics seems warranted.Keywords: Astrocyte, heme, heme oxygenase, intracerebral hemorrhage, Nrf2, Stroke.
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CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"article" as access_level, j.issue_id, j.article_id from `user_access_article_token` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 60014946 and j.to_ip >=60014946 )) and ((j.from_date <= 1738024875 and j.to_date >= 1738024875 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.article_id = 79329)
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select * from `article` where `first_page` < '2226' and is_uploaded = 1 and issue_id = 7737 order by cast(first_page as SIGNED) desc limit 1
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select * from `article` where `last_page` > '2237' and is_uploaded = 1 and issue_id = 7737 order by cast(first_page as SIGNED) asc limit 1
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select `language_id` from `multilanguage` where `short_code` = 'en'
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select `source_lang_label`, `target_lang_label` from `multilanguage_labels` where `target_lang_id` = 1
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select `id` from `multilanguage_article` where `article_id` = 79329 limit 1
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select b.banner_link, b.banner_name, b.banner_script, b.banner_remarks, b.banner_file_name, b.banner_placement, bd.content_type, bd.content_id from `tbl_banner` as `b` inner join `tbl_banner_detail` as `bd` on `bd`.`banner_id` = `b`.`banner_id` inner join `users` as `u` on `u`.`id` = `b`.`updated_by` inner join `journal` as `j` on `j`.`journal_id` = `bd`.`content_id` where `b`.`banner_journal` = 1 and `bd`.`content_type` = 'J' and `bd`.`content_id` = 29 and `b`.`banner_from_date` <= 1738024875 and `b`.`banner_to_date` >= 1738024875 and `b`.`banner_status` = 'A' order by `b`.`banner_id` desc
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select count(*) as aggregate from `uc_cart_products` where cart_id='b23e355198fc9b59cc56a30817afc73a'
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|
200
[]
[]
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