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• W4232376772 abstract "Abstract Background: Hypoxic-ischemia (HI) is a major cause of acquired visual impairment in children of developed countries. Previous studies have shown that systemic administration of 7,8-dihydroxyflavone (DHF), a selective tropomyosin receptor kinase B (TrkB) agonist, provided long-term neuroprotection against HI injury in immature retina. However, the target genes and the mechanisms of the neuroprotective effects of TrkB signaling are not known. Methods: HI retinal injury was induced by unilateral common carotid artery ligation followed by 8% oxygen for 2 hrs at P7 rat pups. DHF was administered intraperitoneally at 2 hrs before and 18 hrs after HI injury. Polymerase chain reaction (PCR) array was used to identify genes upregulated after DHF treatment, then confirmed with quantitative real-time reverse transcriptase PCR and Western blot. Effects of the downstream mediator of DHF were assessed by intravitreal injection of neutralizing antibody at 4 hrs after DHF administration (24 hrs after HI). Meanwhile, the target protein was injected into the vitreous at 24 hrs after HI to validate its protective effect when exogenously supplemented. The outcomes were assessed by electroretinography and by histopathological sections of the rat retina. Results: Systemic DHF treatment after HI significantly increased the expression of artemin (ARTN) gene and protein at P8 and P10, respectively. The neuroprotective effects of DHF were inhibited after the blockade of ARTN protein with an increase in neuroinflammation and astrogliosis. ARTN treatment showed long-term protection against HI injury at both the histopathological and functional levels. The neuroprotective effects of ARTN were related to a decrease in microglial activation at P17, and attenuation of astrogliosis at P29. ARTN enhances phosphorylation of RET, ERK, and JNK, but not AKT or p38 in the immature retina. Conclusions: Neuroprotective effect of TrkB agonist is partially exerted through a mechanism that involves ARTN because the protective effect is ameliorated by ARTN sequestration. ARTN treatment after HI injury protects the immature retina by attenuating the late neuroinflammation and astrogliosis in the immature retina via ARTN/RET/JNK/ERK signaling pathway. ARTN can be a strategy to provide long-term protection in immature retina against HI injury." @default.
• W4232376772 created "2022-05-12" @default.
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• W4232376772 date "2020-12-01" @default.
• W4232376772 modified "2023-09-28" @default.
• W4232376772 title "Artemin is Upregulated by TrkB agonist and Protects the Immature Retina against Hypoxic-ischemic Injury by Suppressing Neuroinflammation and Astrogliosis" @default.
• W4232376772 doi "https://doi.org/10.21203/rs.3.rs-115996/v1" @default.
• W4232376772 hasPublicationYear "2020" @default.
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