Dexmedetomidine pretreatment alleviates cerebral ischemia/reperfusion injury by inhibiting neuroinflammation through the JAK2/STAT3 pathway

Liu, Huan; Li, Jianli; Jiang, Li; He, Jinhua; Zhang, Huanhuan; Wang, Keyan

doi:10.1590/1414-431x2022e12145

Cited by 10 publications

(5 citation statements)

References 29 publications

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“…It was reported that Dex could attenuate neuronal injury induced by cerebral ischemia-reperfusion by regulating miR-199a [ 9 ]. Dex pretreatment alleviated cerebral ischemia/reperfusion injury by inhibiting neuroinflammation through the JAK2/STAT3 pathway [ 8 ]. However, the specific targeting molecule has not been unfolded.…”

Section: Discussionmentioning

confidence: 99%

“…Dexmedetomidine (Dex) is a highly selective α2-adrenergic receptor agonist, with central anti sympathetic effect, can produce sedative, analgesic, and anti-anxiety effects [ 8 , 9 ]. Dex has no obvious inhibitory effect on respiration, and it is widely used in clinical practice [ 10 ].…”

Section: Introductionmentioning

confidence: 99%

“…Therefore, protecting BBB on the basis of thrombolysis or thrombectomy becomes one of the important therapeutic strategies to improve the prognosis of cerebral ischemia injury. Dexmedetomidine (Dex) is a highly selective α2-adrenergic receptor agonist, with central anti sympathetic effect, can produce sedative, analgesic, and anti-anxiety effects [8,9]. Dex has no obvious inhibitory effect on respiration, and it is widely used in clinical practice [10].…”

Section: Introductionmentioning

confidence: 99%

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Suppression of cerebral ischemia injury induced blood brain barrier breakdown by dexmedetomidine via promoting CCN1

Liu,

Jia,

Liu

et al. 2024

Aging

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Background: Blood-brain barrier (BBB) could aggravate cerebral ischemia injury. Dexmedetomidine (Dex) has been believed to play a protective role in cerebral ischemia injury-induced BBB injury. Methods: Middle cerebral artery occlusion (MCAO) and oxygen-glucose deprivation (OGD) models were established to simulate cerebral ischemia injury. Animal experiments included 4 groups, Sham, MCAO, MCAO+Dex, MCAO+Dex+sh-CCN1. Generally applicable gene set enrichment analysis was performed to analyze gene expression difference. Total collagen content and Evans blue staining were performed to measure infarct ratio and BBB breakdown, respectively. The cell apoptosis, mRNA and protein expression were measured through flow cytometry, PCR, and western blotting, respectively. The levels of IL-1β, TNF-α, and IL-6 in serum were measured with commercial ELISA kits. Results: Dex greatly promoted the expression level of CCN1. Dex suppressed cerebral ischemia injury, increased tight junction protein expression, improved the memory ability and neurological function of MCAO rats through targeting CCN1. The significant increase of inflammatory factors in the serum of MCAO rats were suppressed by Dex. Dex suppressed OGD induced increase of HRP permeability and promoting tight junction protein expression in vitro through regulating CCN1. The neurological function evaluation was performed with Neurological Severity Score (NSS) and Longa Score Scale. Conclusions: Dex could remarkably alleviate cerebral ischemia injury by inhibiting BBB breakdown, inflammatory response, and promoting neurological function and tight junction protein expression via up-regulating CCN1. This study might provide a novel therapeutic target for the prevention and treatment of cerebral ischemia injury-induced BBB.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Suppression of cerebral ischemia injury induced blood brain barrier breakdown by dexmedetomidine via promoting CCN1

Liu,

Jia,

Liu

et al. 2024

Aging

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“…De novo JAK2 and MAPK7 mutations closely associated with ASD have been identified using whole-exome sequencing in Chinese children and adolescent trio samples ( 50 ). Negative regulation of the JAK2/STAT3 signaling pathway can inhibit neuroinflammation ( 51 ). The JAK2/STAT3 signaling pathway regulates microglia/macrophage polarization (toward M2 polarization) during cerebral ischemia reperfusion injury (CIRI), thereby attenuating brain injury.…”

Section: Discussionmentioning

confidence: 99%

Bioinformatics analysis of genomic and immune infiltration patterns in autism spectrum disorder

Wei¹,

Guo²,

Wu³

et al. 2022

Ann Transl Med

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Background: Autism spectrum disorder (ASD) is a specific type of pervasive developmental disorder, and most studies suggest that the onset of autism may be related to genetic and immune factors. The etiology of autism and the underlying molecular events need to be further addressed. Methods:The ASD-related dataset GSE18123 was downloaded from the Gene Expression Omnibus (GEO) database. Gene set enrichment analysis (GSEA) was used to screen for Gene Ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways that may be associated with autism. The top 5,000 genes with an absolute median difference were obtained, and a co-expression network was constructed using weighted correlation network analysis (WGCNA). In addition, GO and KEGG enrichment analyses were performed for genes in the modules most closely related to ASD. Hub genes were found in the significant modules, and the expression values and receiver operating characteristic (ROC) curves of the hub genes were analyzed and validated. Immune cell infiltration in ASD was calculated using the CIBERSORT algorithm, and the relationship between hub genes and immune cells was analyzed. Finally, GSEA was used to explore the potential pathways of hub genes affecting ASD. Results:The 5,000 DEGs were divided into eight significant modules by WGCNA. The green module was most significantly associated with ASD, and two hub genes [fatty acid-binding protein 2 (FABP2) and Janus kinase 2 (JAK2)] were found. Immune cell infiltration showed that resting dendritic cells and monocytes differed significantly in ASD and healthy individuals. FABP2 was significantly associated with memory B cells and CD8 T cells. JAK2 was significantly associated with monocytes, CD4 activated memory T cells, CD4 resting memory T cells, activated dendritic cells, gamma delta T cells, regulatory T cells (Tregs), CD8 T cells, and naïve CD4 T cells. FABP2 and JAK2 were found to affect multiple pathways of immunity.Conclusions: FABP2 and JAK2 may influence the immune microenvironment of ASD by regulating immune cells and immune-related pathways and are candidate molecular markers for the development of ASD.

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“…It was approved for sedation and analgesia in intensive care unit (ICU) patients in the United States in 1999 ( Damian et al, 2020 ). Preclinical studies have shown that DEX can improve IRI in various tissues, including the liver, thus providing organ protection ( Tang et al, 2020 ; Yu et al, 2020 ; Liu et al, 2022 ; Tao et al, 2022 ). However, its effectiveness and safety in IRI of transplanted livers still lack definite conclusions.…”

Section: Introductionmentioning

confidence: 99%

Effect of dexmedetomidine on liver transplantation: a meta-analysis

Jia

Guo

et al. 2023

Front. Pharmacol.

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Background: Dexmedetomidine (DEX), an adjuvant anesthetic, may improve the clinical outcomes of liver transplantation (LT).Methods: We summarized the relevant clinical trials of DEX in patients undergoing LT. As of 30 January 2023, we searched The Cochrane Library, MEDLINE, EMBASE, Clinical Trial.gov and the WHO ICTRP. The main outcomes were postoperative liver and renal function. The random effect model or fixed effect model was used to summarize the outcomes across centers based on the differences in heterogeneity.Results: The meta-analysis included nine studies in total. Compared with the control group, the DEX group had a reduced warm ischemia time (MD-4.39; 95% CI-6.74−2.05), improved postoperative liver (peak aspartate transferase: MD-75.77, 95% CI-112.81−38.73; peak alanine transferase: MD-133.51, 95% CI-235.57−31.45) and renal function (peak creatinine: MD-8.35, 95% CI-14.89−1.80), and a reduced risk of moderate-to-extreme liver ischemia-reperfusion injury (OR 0.28, 95% CI 0.14-0.60). Finally, the hospital stay of these patients was decreased (MD-2.28, 95% CI-4.00−0.56). Subgroup analysis of prospective studies showed that DEX may have better efficacy in living donors and adult recipients.Conclusion: DEX can improve short-term clinical outcomes and shorten the hospital stay of patients. However, the long-term efficacy of DEX and its interfering factors deserves further study.Systematic Review: identifier CRD42022351664.

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Dexmedetomidine pretreatment alleviates cerebral ischemia/reperfusion injury by inhibiting neuroinflammation through the JAK2/STAT3 pathway

Cited by 10 publications

References 29 publications

Suppression of cerebral ischemia injury induced blood brain barrier breakdown by dexmedetomidine via promoting CCN1

Suppression of cerebral ischemia injury induced blood brain barrier breakdown by dexmedetomidine via promoting CCN1

Bioinformatics analysis of genomic and immune infiltration patterns in autism spectrum disorder

Effect of dexmedetomidine on liver transplantation: a meta-analysis

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