Dexmedetomidine Alleviates Hypoxic-Ischemic Brain Damage in Neonatal Rats Through Reducing MicroRNA-134-5p-Mediated NLRX1 Downregulation |
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| Institution: | 1. Department of Neurology, Tohoku Medical and Pharmaceutical University Hospital, 1-15-1 Fukumuro, Miyagino-ku, Sendai, Miyagi, 983-8536, Japan;2. Department of Stroke Neurology, Kohnan Hospital, 4-20-1 Nagamachi-minami, Taihaku-ku, Sendai, Miyagi, 982-8523, Japan;1. Department of Neurology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China;2. Department of Clinical Epidemiology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China;1. Department of Neurosurgery, Albert Einstein College of Medicine, Montefiore Medical Center, Bronx NY USA;2. Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Montefiore Medical Center, Bronx NY USA;1. New York Medical College School of Medicine, Valhalla, NY, USA;2. Department of Neurosurgery, Westchester Medical Center at New York Medical College, 100 Woods Road, Valhalla, NY 10595, USA;3. Department of Neurology, Westchester Medical Center at New York Medical College, Valhalla, NY, USA;1. Department of Neurology, Neurosciences Institute, Atrium Health, 1000 Blythe Blvd, Charlotte, NC 28203, USA;2. Information and Analytics Services, Atrium Health, Charlotte, NC, USA;3. Neurosciences Institute, Atrium Health, Charlotte, NC, USA;4. Department of Emergency Medicine, Neurosciences Institute, Atrium Health, Charlotte, NC, USA |
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| Abstract: | BackgroundDexmedetomidine (Dex) is a safe and effective anesthetic adjunct which also has neuroprotective roles. This study aimed to validate the role of Dex in hypoxic-ischemic brain damage (HIBD) in neonatal rats and the functional molecules.MethodsA neonatal rat model of HIBD was established and treated with Dex. The learning and memory abilities of rats were determined by Morris water maze tests. The left-hemisphere encephalatrophy, pathological changes, neuronal apoptosis, and inflammation in rat hippocampal tissues were examined to evaluate the treating effects of Dex on HIBD. Differentially expressed microRNAs (miRNAs) in rats with HIBD were screened using microarray analysis. Potential downstream molecules mediated by miR-134-5p were predicted using bioinformatics analysis. Altered expression of miR-134-5p and NLR family member X1 (NLRX1) was induced in rats after Dex treatment for rescue experiments.ResultsDex treatment significantly enhanced the learning and memory abilities of rats and reduced encephalatrophy in rats. It also alleviated pathological changes, neuronal apoptosis, and the production of pro-inflammatory cytokines in rat hippocampal tissues. miR-134-5p was significantly upregulated in rats with HIBD. Dex treatment reduced the expression of miR-134-5p. NLRX1 was a target gene of miR-134-5p and it reduced the phosphorylation of IκBα and p65, namely the activation of NF-κB signaling. Overexpression of miR-134-5p blocked, whereas overexpression of NLRX1 strengthened the protective effects of Dex on neonatal rats.ConclusionThis study demonstrates that Dex treatment can alleviate HIBD in neonatal rats through restoring NLRX1 expression by suppressing miR-134-5p. |
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