Effects of intraoperative low-dose esketamine on postoperative pain after vestibular schwannoma resection: A prospective randomized, double-blind, placebo-controlled study.

AIMS: Esketamine may reduce acute postoperative pain in several settings. However, the effects of low-dose esketamine on postoperative pain after vestibular schwannoma (VS) resection with propofol/remifentanil total intravenous anaesthesia (TIVA) are unclear. The aim of this study is to observe the effects of intraoperative low-dose esketamine on postoperative pain after vestibular schwannoma resection. METHODS: This single-centre, randomized, placebo-controlled, double-blind trial included 90 adults undergoing VS resection via the retrosigmoid approach with TIVA. The patients were randomly allocated to two groups: esketamine or control (n = 45 in each group). Patients received low-dose esketamine (0.2 mg/kg) or a similar volume of normal saline after dural closure. The primary outcome was the pain score during movement (gentle head movement) at 24 h postoperatively. Secondary outcomes included recovery time, bispectral index (BIS) values and haemodynamic profiles during the first 30 min after esketamine administration, and adverse effects. RESULTS: Low-dose esketamine did not reduce pain scores at rest (P > .05) or with movement (P > .05) within the first 24 h after surgery. Esketamine moderately increased BIS values for at least 30 min after administration (P < .0001) but did not affect heart rate (P = .992) or mean arterial blood pressure (P = .994). Esketamine prolonged extubation time (P = .042, 95% confidence interval: 0.08 to 4.42) and decreased the effect-site concentration of remifentanil at extubation (P = .001, 95% confidence interval: -0.53 to -0.15) but did not affect the time to resumption of spatial orientation. Postoperative nausea and vomiting rates did not differ between groups, and no hallucinations or excessive sedation was observed. CONCLUSION: Intraoperative low-dose esketamine did not significantly reduce acute pain after VS resection with propofol/remifentanil TIVA. However, BIS values increased for at least 30 min after esketamine administration.

miR-506-3p Relieves Neuropathic Pain following Brachial Plexus Avulsion via Mitigating Microglial Activation through Targeting the CCL2-CCR2 Axis.

Neuroinflammation results in neuropathic pain (NP) following brachial plexus avulsion (BPA). This research was designed for investigating the function of miR-506-3p in BPA-induced NP. A total brachial plexus root avulsion model was produced in adult rats as well as IL-1ß-treated motoneuron-like NSC-34 cells and the LPS-treated microglia cell line BV2 for in vivo and in vitro experiments, respectively. RT-PCR and Western blot were performed to detect the profiles of miR-506-3p, CCL2 and CCR2, NF-κB, FOXO3a, TNF-α, IL-1ß, and IL-6 in cells or the spinal cord close to the tBPI lesion. Neuronal apoptosis was evaluated by immunohistochemistry in vivo. CCK8, TUNEL staining, and the lactic dehydrogenase kit were adopted for the evaluation of neuronal viability or damage in vitro. RNA immunoprecipitation and dual luciferase reporter gene assays analyzed the targeted association between miR-506-3p and CCL2. As shown by the data, miR-506-3p was vigorously less expressed, while CCL2-CCR2, NF-κB TNF-α, IL-1ß, and IL-6 were upregulated in the spinal cord with tBPI. Overexpression of miR-506-3p attenuated neuronal apoptosis and microglial inflammation. Mechanistically, CCL2 was a downstream target of miR-506-3p. Upregulating miR-506-3p dampened CCL2-CCR2 and NF-κB activation in the spinal cord and microglia. miR-506-3p had neuroprotective and inflammation-fighting functions in the tBPI rat model via CCL2/CCR2/NF-κB axis.

Long Non-Coding RNA BACE1-AS Modulates Isoflurane-Induced Neurotoxicity to Alzheimer's Disease Through Sponging miR-214-3p.

Isoflurane, an anesthetic, can aggravate the progression of Alzheimer's disease (AD). Long non-coding RNA ß-secretase 1 (BACE1)-antisense transcript (BACE1-AS) and miR-214-3p are related to AD progression. Nevertheless, it is unclear whether BACE1-AS is involved in the development of isoflurane-mediated AD via miR-214-3p. Amyloid beta peptide (Aß) was employed to construct the AD cell model. The expression of BACE1-AS and miR-214-3p in the plasma of AD patients and SK-N-SH and SK-N-AS cells treated with Aß and isoflurane was assessed through quantitative reverse transcription polymerase chain reaction (qRT-PCR). The proliferation and apoptosis of Aß-treated SK-N-SH and SK-N-AS cells were determined via 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) or flow cytometry assays, respectively. Protein levels of B cell lymphoma 2 (Bcl-2), Bcl-2-associated X (Bax), CyclinD1, microtubule-associated protein A1/1B-light chain3 (LC3 I/LC3 II), p62 and Beclin1 were detected via western blot analysis. The relationship between BACE1-AS and miR-214-3p was verified by dual-luciferase reporter assay. We found that BACE1-AS was upregulated and miR-214-3p was downregulated in the plasma of AD patients and SK-N-SH and SK-N-AS cells treated with Aß and isoflurane. Both BACE1-AS depletion and miR-214-3p augmentation restored the suppression of proliferation and the facilitation of apoptosis and autophagy of Aß-treated SK-N-SH and SK-N-AS cells induced by isoflurane. Importantly, BACE1-AS acted as a sponge for miR-214-3p. Additionally, miR-214-3p silencing reversed the influence of BACE1-AS knockdown on isoflurane-mediated proliferation, apoptosis and autophagy in Aß-induced SK-N-SH and SK-N-AS cells. In conclusion, BACE1-AS aggravated isoflurane-induced neurotoxicity to AD via sponging miR-214-3p.

MicroRNA-582-5p Reduces Propofol-induced Apoptosis in Developing Neurons by Targeting ROCK1.

BACKGROUND: Propofol is an intravenous drug commonly used in anesthesia procedures and intensive care in children. However, it also has neurotoxic effects on children. MicroRNA plays an important role in neurological diseases and neurotoxicity. METHODS: In this study, primary rat hippocampal neurons were used to investigate the role of miR- 582-5p in propofol-induced neurotoxicity. Cell viability was monitored by 3-(4,5-dimethylthiazolyl)- 2,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, while the expression of proteins was monitored by real-time quantitation polymerase chain reaction (RT-qPCR) and western blot. TargetScan and double luciferase report assay were used to predict the targeting relationship between miR-582-5p and Rho-associated serine-threonine protein kinase 1 (ROCK1). RESULTS: In the present study, the viability of neurons and the expression of miR-582-5p were decreased in a time-dependent manner after propofol treatment. Besides, miR-582-5p overexpression significantly reduced the toxicity of propofol on neuron cells but had no significant effect on normal nerve cells. In addition, miR-582-5p overexpression significantly reversed the expression of apoptosis-related proteins (cleaved caspase 3 and cleaved caspase 9) induced by propofol but had no significant effect in normal nerve cells. TargetScan and Dual-luciferase report assay revealed that ROCK1 was a targeted regulatory gene for miR-582-5p, and propofol treatment up-regulated ROCK1 expression by inhibiting miR-582-5p expression. Notably, miR-582-5p overexpression significantly increased cell viability, while ROCK1 overexpression reversed the effect of miR-582- 5p. CONCLUSION: Taken together, these findings suggest that miR-582-5p alleviated propofol-induced apoptosis of newborn rat neurons by inhibiting ROCK1.