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566982 occurrences (No.17 in the rank) during 5 years in the PubMed. [cache]

343) Currently, whether immunoresponsive gene 1/itaconate axis exerts a modulatory effect in ischaemic stroke remains unexplored.

--- ABSTRACT ---

PMID:34557667 DOI:10.1093/braincomms/fcab187

2021 Brain communications

* Immunoresponsive gene 1 modulates the severity of brain injury in cerebral ischaemia.

- Inflammatory stimuli induce immunoresponsive gene 1 expression that in turn catalyses the production of itaconate through diverting cis-aconitate away from the tricarboxylic acid cycle. The immunoregulatory effect of the immunoresponsive gene 1/itaconate axis has been recently documented in lipopolysaccharide-activated mouse and human macrophages. In addition, dimethyl itaconate, an itaconate derivative, was reported to ameliorate disease severity in the animal models of psoriasis and multiple sclerosis. Currently, whether immunoresponsive gene 1/itaconate axis exerts a modulatory effect in ischaemic stroke remains unexplored. In this study, we investigated whether immunoresponsive gene 1 plays a role in modulating ischaemic brain injury. In addition, the molecular mechanism underlying the protective effects of immunoresponsive gene 1 in ischaemic stroke was elucidated. Our results showed that immunoresponsive gene 1 was highly induced in the ischaemic brain following ischaemic injury. Interestingly, we found that IRG1^-/- stroke animals exhibited exacerbated brain injury, displayed with enlarged cerebral infarct, compared to wild-type stroke controls. Furthermore, IRG1^-/- stroke animals presented aggravated blood-brain barrier disruption, associated with augmented Evans blue leakage and increased immune cell infiltrates in the ischaemic brain. Moreover, IRG1^-/- stroke animals displayed elevated microglia activation, demonstrated with increased CD68, CD86 and Iba1 expression. Further analysis revealed that immunoresponsive gene 1 was induced in microglia after ischaemic stroke, and deficiency in immunoresponsive gene 1 resulted in repressed microglial heme oxygenase-1 expression and exacerbated ischaemic brain injury. Notably, the administration of dimethyl itaconate to compensate for the deficiency of immunoresponsive gene 1/itaconate axis led to enhanced microglial heme oxygenase-1 expression, alleviated ischaemic brain injury, improved motor function and decreased mortality in IRG1^-/- stroke animals. In summary, we demonstrate for the first time that the induction of immunoresponsive gene 1 in microglia following ischaemic stroke serves as an endogenous protective mechanism to restrain brain injury through heme oxygenase-1 up-regulation. Thus, our findings suggest that targeting immunoresponsive gene 1 may represent a novel therapeutic approach for the treatment of ischaemic stroke.

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(1)219 of	(8)11 sizes	(15)3 to	(22)2 measure
(2)66 on	(9)9 is	(16)3 via	(23)2 relationship
(3)30 null	(10)4 against	(17)3 with	(24)2 than
(4)20 and	(11)4 for	(18)2 P	(25)2 trials
(5)19 in	(12)4 such	(19)2 at
(6)16 was	(13)4 that	(20)2 estimates,
(7)13 size	(14)3 may	(21)2 induced

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--- WordNet output for effect --- =>趣旨, 結果, 影響, 効力, 活動, 印象, 効果, 成し遂げる Overview of noun effect The noun effect has 6 senses (first 5 from tagged texts) 1. (101) consequence, effect, outcome, result, event, issue, upshot -- (a phenomenon that follows and is caused by some previous phenomenon; "the magnetic effect was greater when the rod was lengthwise"; "his decision had depressing consequences for business"; "he acted very wise after the event") 2. (11) impression, effect -- (an outward appearance; "he made a good impression"; "I wanted to create an impression of success"; "she retained that bold effect in her reproductions of the original painting") 3. (9) effect -- (an impression (especially one that is artificial or contrived); "he just did it for effect") 4. (2) effect, essence, burden, core, gist -- (the central meaning or theme of a speech or literary work) 5. (1) effect, force -- ((of a law) having legal validity; "the law is still in effect") 6. effect -- (a symptom caused by an illness or a drug; "the effects of sleep loss"; "the effect of the anesthetic") Overview of verb effect The verb effect has 2 senses (first 2 from tagged texts) 1. (17) effect, effectuate, set up -- (produce; "The scientists set up a shock wave") 2. (3) effect -- (act so as to bring into existence; "effect a change") --- WordNet end ---