Retracted: microRNA-129-5p involved in the neuroprotective effect of dexmedetomidine on hypoxic-ischemic brain injury by targeting COL3A1 through the Wnt/ß-catenin signaling pathway in neonatal rats.

Our study aims to elucidate the mechanisms how microRNA-129-5p (miR-129-5p) involved in the neuroprotective effect of dexmedetomidine (DEX) on hypoxic-ischemic brain injury (HIBI) by targeting the type III procollagen gene (COL3A1) through the Wnt/ß-catenin signaling pathway in neonatal rats. A total of 120 rats were obtained, among which 15 rats were selected as sham group and rest rats as model, DEX, DEX + negative control (DEX + NC), DEX + miR-129-5p mimics, DEX + miR-129-5p inhibitors, DEX + XAV-939, and DEX + miR-129-5p inhibitors + XAV-939 groups. A dual-luciferase reporter assay was performed for the target relationship between miR-129-5p and COL3A1. Weight rate and water content of cerebral hemisphere were detected. Quantitative real-time polymerase chain reaction and Western blot analysis were conducted to detect miR-129-5p expression and expressions of COL3A1, E-cadherin, T-cell factor (TCF)- 4, and ß-catenin. The DEX, DEX + miR-129-5p mimics, DEX + XAV-939 groups had increased weight rate of the cerebral hemisphere, but decreased water content of left cerebral hemisphere, levels of COL3A1, ß-catenin, TCF-4, and E-cadherin in the hippocampus compared with the model and DEX + miR-129-5p inhibitors groups. COL3A1 was verified as the target gene of the miR-129-5p. Compared with the DEX + NC and DEX + miR-129-5p inhibitors + XAV-939 groups, the DEX + XAV-939 and DEX + miR-129-5p mimics groups had elevated weight rate of the cerebral hemisphere, but reduced water content of left cerebral hemisphere, levels of COL3A1, ß-catenin, TCF-4, and E-cadherin in the hippocampus. Our findings demonstrate that miR-129-5p improves the neuroprotective role of DEX in HIBI by targeting COL3A1 through the Wnt/ß-catenin signaling pathway in neonatal rats.

Silencing of long noncoding RNA MEG3 enhances cerebral protection of dexmedetomidine against hypoxic-ischemic brain damage in neonatal mice by binding to miR-129-5p.

Hypoxic-ischemic brain damage (HIBD) is a leading cause of neonatal acute mortality and chronic nervous system injury. Recently, it has been found that long noncoding RNAs (lncRNAs) play a significant role in the neurodevelopment and etiopathogenesis of HIBD. Here, the researchers aimed to determine the role of lncRNA maternally expressed gene (MEG3) in the therapeutic effect of dexmedetomidine (DEX) in neonatal mice with HIBD through the regulation of microRNA-129-5p (miR-129-5p). HIBD models were established in C57/BL6 neonatal mice. Subsequently, the target relationship between MEG3 and miR-129-5p was predicted and verified. The neonatal mice were injected with DEX, ad-shMEG3, and mimics and inhibitors of miR-129-5p to identify roles of MEG3 and miR-129-5p in therapeutic effects of DEX on neuronal apoptosis and injury, cerebral atrophy, and learning and memory ability of neonatal mice with HIBD. MEG3 directly targeted and inhibited the expression of miR-129-5p. Silencing of MEG3 or upregulation of miR-129-5p effectively promoted the therapeutic effect of DEX on neonatal mice with HIBD. Silencing of MEG3 or upregulation of miR-129-5p reduced the neuronal apoptosis rate and degree of cerebral atrophy, and also enhanced the learning and memory ability of HIBD neonatal mice. Collectively, the key findings obtained from the present study support the notion that MEG3 silencing enhances the therapeutic effect of DEX on neonatal mice with HIBD by binding to miR-129-5p.

Neuroprotective effects of dexmedetomidine on traumatic brain injury: Involvement of neuronal apoptosis and HSP70 expression.

The aim of the present study was to investigate the protective effect of dexmedetomidine (Dex) on traumatic brain injury (TBI), and further evaluate whether the underlying neuroprotective mechanisms are associated with neurological apoptosis and the expression of 70 kDa heat shock protein (HSP70) in the hippocampus. A total of 90 adult male Sprague­Dawley rats were randomly assigned into 3 groups (n=30/group): Sham, TBI and Dex groups. The rat models of TBI were established using a modified weight­drop device and Dex (15 µg/kg) was intravenously administered immediately following TBI. The brain edema and neurological function outcomes of TBI were assessed using wet­dry weight analysis and the Neurological Severity Score method. The expression levels of B­cell lymphoma­2 (Bcl­2) and Bcl­2­associated X protein (Bax) in the rat hippocampus were evaluated using immunohistochemical staining and western blot analysis. The protein levels of HSP70 in the hippocampal region were analyzed using western blot analysis. The results of the present study revealed that administration of Dex post­TBI improved brain edema and neurological outcomes, due to the attenuation of the TBI­induced reduction of Bax expression and increase of Bcl­2 and HSP70 expression. In conclusion, the results of the present study suggested that administration of Dex may serve as a neuroprotective agent against brain injury, at least partially via the inhibition of neuronal apoptosis and upregulation of HSP70 expression in the hippocampus.

Dexmedetomidine exerts neuroprotective effect via the activation of the PI3K/Akt/mTOR signaling pathway in rats with traumatic brain injury.

OBJECTIVE: This study aims to explore the neuroprotective effects of dexmedetomidine (Dex) in rats suffering from traumatic brain injury (TBI) via the PI3K/Akt/mTOR signaling pathway. METHODS: A weight drop model was performed for TBI model establishment. A total of 150 Sprague Dawley rats were selected and assigned into control, sham, TBI, TBI+Dex, TBI+LY294002 (LY) and TBI+Dex+LY groups. Modified Neurological Severity Score (mNSS) was conducted in order to evaluate the neurological injury. The water content in brain tissues was measured. The expressions of PI3K/Akt/mTOR signaling pathway-related proteins, tight junction proteins (ZO-1 and Claudin-5) and autophagy proteins (LC3 I/II and Beclin-1) were detected using Western blot assay. A TUNEL assay was applied for cell apoptosis, immunofluorescence was employed for the detection of the positive expression of LC3, and ELISA was applied for detection of levels of inflammatory factors [tumor necrosis factor-alph (TNF-a), interleukin-1ß (IL-1ß), interferon-γ (INF-γ) as well as IL-6], respectively. RESULTS: Compared with the control group, the other four groups exhibited increased mNSS, brain water content, expression of LC3, TNF-a, IL-1ß, INF-γ and IL-6, and positive expression of LC3, expression of LC3 I/II and Beclin-1, but decreased expression of pp-PI3K/t-PI3K, p-Akt/t-Akt, p-mTOR/t-mTOR, ZO-1 and Claudin-5. Compared with the TBI group, the TBI+Dex group exhibited reduced mNSS, brain water content, expression of LC3, TNF-a, IL-1ß, INF-γ and IL-6, positive expression of LC3, as well as expression of LC3 I/II and Beclin-1 but demonstrated an elevated expression of pp-PI3K/t-PI3K, p-Akt/t-Akt, p-mTOR/t-mTOR, ZO-1 and Claudin-5, while opposite trends were observed in the TBI+LY group. The TBI+Dex group exhibited reduced mNSS, brain water content, expression of LC3, TNF-a, IL-1ß, INF-γ and IL-6, positive expression of LC3, as well as expression of LC3 I/II and Beclin-1 but demonstrated an elevated expression of pp-PI3K/t-PI3K, p-Akt/t-Akt, p-mTOR/t-mTOR, ZO-1 and Claudin-5, while opposite trends were observed in the TBI+LY group, as compared with the TBI+Dex+LY group. CONCLUSION: The data shows that Dex exerts a neuroprotective effect via the activation of the PI3K/Akt/mTOR signaling pathway in rats with TBI.