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- Chen, Y, et al.
(författare)
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miR-124/VAMP3 is a novel therapeutic target for mitigation of surgical trauma-induced microglial activation
- 2019
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Ingår i: Signal transduction and targeted therapy. - : Springer Science and Business Media LLC. - 2059-3635. ; 4, s. 27-
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Tidskriftsartikel (refereegranskat)abstract
- Activation of microglia and the subsequently elevated inflammatory cytokine release in the brain during surgery predispose individuals to cognitive dysfunction, also known as postoperative cognitive dysfunction (POCD). miR-124 is one of the most abundant microRNAs in the brain that regulates microglial function. Elucidating the role of miR-124 in microglial activation in the context of surgery may therefore promote understanding of as well as therapeutic development for post-surgical disorders involving microglial activation. The downstream targets of miR-124 were investigated using bioinformatic screening and dual-luciferase reporter assay validation, and vesicle-associated membrane protein 3 (VAMP3) was identified as a potential target. The kinetics of miR-124/VAMP3 expression was first examined in vitro in microglial cells (primary microglia and BV2 microglial cells) following lipopolysaccharide (LPS) stimulation. LPS induced a time-dependent decrease of miR-124 and upregulated the expression of VAMP3. Manipulating miR-124/VAMP3 expression by using miR-124 mimics or VAMP3-specific siRNA in LPS-stimulated BV2 microglial cells inhibited BV2 microglial activation-associated inflammatory cytokine release. To further examine the role of miR-124/VAMP3 in a surgical setting, we employed a rat surgical trauma model. Significant microglial activation and altered miR-124/VAMP3 expression were observed following surgical trauma. We also altered miR-124/VAMP3 expression in the rat surgical trauma model by administration of exogenous miR-124 and by using electroacupuncture, which is a clinically applicable treatment that modulates microglial function and minimizes postoperative disorders. We determined that electroacupuncture treatment specifically increases the expression of miR-124 in the hypothalamus and hippocampus. Increased miR-124 expression with a concomitant decrease in VAMP3 expression resulted in decreased inflammatory cytokine release related to microglial activation post-surgery. Our study indicates that miR-124/VAMP3 is involved in surgery-induced microglial activation and that targeting miR-124/VAMP3 could be a potential therapeutic strategy for postoperative disorders involving microglial activation.
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- He, BH, et al.
(författare)
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The Correlation of a 2D Volume-Referencing Endolymphatic-Hydrops Grading System With Extra-Tympanic Electrocochleography in Patients With Definite Ménière's Disease
- 2021
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Ingår i: Frontiers in neurology. - : Frontiers Media SA. - 1664-2295. ; 11, s. 595038-
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Tidskriftsartikel (refereegranskat)abstract
- Background: Although magnetic resonance imaging (MRI) of the membranous labyrinth and electrocochleography (ECochG) have been used to diagnose endolymphatic hydrops (ELH) in patients with Ménière's disease (MD), the relationship between imaging and ECochG is not well-documented.Objectives: This study evaluates the ELH using 3D-FLAIR MRI and extra-tympanic ECochG (ET-ECochG) and correlates the results from 3D-FLAIR MRI to those from ET-ECochG.Materials and Methods: 3D-FLAIR MRI images of 50 patients were assessed using a 2D volume-referencing grading system (VR scores, relative scores according to the known volumes of the cochlea, vestibule, and semicircular canals). Forty healthy subjects were included and compared to 51 definite MD ears of 50 patients while analyzing the ET-ECochG, which used a self-made bronze foil electrode. The amplitude ratio of the summating potential (SP) to the action potential (AP) (SP/AP) and the area ratio of SP to AP (Asp/Aap) were collected. Relative ELH grade scores were then correlated to ET-ECochG (SP/AP, Asp/Aap).Results: The VR scores showed a better correlation (r = 0.88) with the pure tone average (PTA), disease duration, and vertigo frequency of MD than the Bernaerts scores (grading the cochlea and vestibule separately) (r = 0.22). The SP/AP and Asp/Aap of the unilateral MD patients were statistically comparable to those measured in contralateral ears and the results between the definite MD ears with healthy ears were statistically comparable (p < 0.05). In a ROC analysis Asp/Aap (area under curve, AUC 0.98) significantly (p = 0.01) outperformed SP/AP (AUC 0.91). The total score of ELH, vestibular ELH, and cochlear ELH were also correlated with SP/AP and Asp/Aap. The strongest correlation was found between the Asp/Aap and cochlear ELH (r = 0.60).Conclusion: The 2D volume-referencing grading system was more meaningful than the Bernaerts scores. A correlation was found between ELH revealed by 3D-FLAIR MRI and the SP/AP of ET-ECochG in evaluating definite MD patients. The Asp/Aap appeared a more sensitive and reliable parameter than SP/AP for diagnosing the ELH of the membranous labyrinth.
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