Isoflurane triggers the acute cognitive impairment of aged rats by damaging hippocampal neurons via the NR2B/CaMKII/CREB pathway.

Isoflurane was responsible for acute neuronal impairment, but its potential molecular mechanisms in damaging hippocampal neurons had not been clearly understood. This study aimed to explore the underlying mechanism of how isoflurane affected the cognitive function of aged rats by damaging the hippocampal neurons. Acute cognitive impairment was found in aged Wistar rats via Morris water maze test and Y-maze test after isoflurane anesthesia in a dose-dependent manner compared with the control group in vivo. Isoflurane also decreased the viabilities and strengthened the apoptotic potential of hippocampal neurons by damaging the mitochondria in a time-dependent manner compared with the control group which was reported by MTT, immunofluorescent assay, flow cytometry and western blot assay in vitro. Isoflurane jeopardized hippocampal neurons by directly inactivating the NR2B/CaMKII/CREB pathway and its harmful effects could be ameliorated by adding CaMKII activator CdCl2. These findings provided evidence that the cognitive ability of aged rats was injured by isoflurane exposure and isoflurane also inhibited the viability and enhanced the apoptosis of hippocampal neurons by damaging the mitochondria through inhibition of the NR2B/CaMKII/CREB pathway and its harmful roles could be partially ameliorated by CdCl2. Our study demonstrated that isoflurane could cause acute neuronal damage and we provided fresh insights that contributed to the safe use of anesthetic agents and the prevention of PND in elderly people.

A rare anaesthetic challenge in a one-lung ventilated paediatric patient with right upper lobe tracheal bronchus.

A tracheal bronchus is a rare congenital anomaly, suggesting abnormal bronchial development. The prevalence of tracheal bronchus in children who undergo bronchoscopy is estimated to be between 0.2% and 3%. When associated with recurrent infection, lobes of the lung must be removed to avoid further lung injury. In such cases, perioperative one-lung ventilation and airway management remain a huge challenge for anaesthesiologists. The case of this rare airway anatomic abnormality in a paediatric patient with two bronchial openings into the right upper lobe, and with a history of recurrent pneumonia, is reported. In addition to a normal opening, a distinct opening in the upper lobe of the right lung was observed, that originated directly from the trachea, superior to the carina. The entire right lung was deflated by left-lung ventilation using a single lumen tracheal tube, and the patient underwent right upper lobe resection. No anaesthesia complications were observed during recovery. In this case, timely identification of the tracheal bronchus and successful collapse of the right lung were key points in the anaesthesia management of this patient.

Berberine Attenuates Arterial Plaque Formation in Atherosclerotic Rats with Damp-Heat Syndrome via Regulating Autophagy.

PURPOSE: Berberine (BBR) is an effective component of Huanglian and has shown to attenuate atherosclerosis (AS); however, the detailed mechanism of BBR-mediated protective actions against AS remains elusive. This study was undertaken to examine the effects of BBR on aortic atherosclerotic plaque stability and the expression of autophagy-related proteins in AS rats with damp-heat syndrome or yang deficiency. METHODS: Thirty SD rats were randomly divided into (1) control (CON); (2) damp-heat syndrome atherosclerosis (AS + DH); (3) yang deficiency syndrome atherosclerosis (AS + YX); (4) damp-heat syndrome atherosclerosis + BBR (AS + DH + BBR); (5) yang deficiency syndrome, atherosclerosis + BBR (AS + YX + BBR); and (6) damp-heat syndrome, atherosclerosis + BBR + 3-methyladenine (AS + DH + BBR + 3-MA) (n = 5/group) groups. Pathological morphology, macrophage plaque infiltration, inflammation, and LC3-II and P62 expression were assessed. RESULTS: Compared with the CON group, the AS + DH and AS + YX groups had an increased plaque area in the aortic tissue with substantial foam cell and macrophage infiltration, and increased levels of IL-1ß and TNF-α (P < 0.01). After four weeks of BBR intervention, the plaque area in the AS + DH + BBR group was reduced with decreased foam cells and macrophage infiltration, and decreased levels of TNF-α and IL-1ß, whereas LC3-II protein expression was increased and P62 protein expression was decreased in the AS + DH + BBR group when compared to AS + DH group. In addition, the AS + DH + BBR + 3-MA group exhibited a significantly enlarged plaque, substantial foam cell and macrophage infiltration, increased levels of IL-1ß and TNF-α, and decreased LC3-II and P62 (P < 0.01) expression when compared to the AS + DH + BBR group. CONCLUSION: Our results indicated that the BBR could inhibit arterial plaque formation and alleviate the inflammatory response in the aortic tissues in the AS rats with damp-heat syndrome possibly via promoting autophagy. The molecular mechanisms of BBR-mediated protective effects in this animal model still require further investigation.

The analgesic efficiency of pregabalin for the treatment of postoperative pain in total hip arthroplasty: A randomized controlled study protocol.

BACKGROUND: Only few studies have yet investigated whether perioperative administration of pregabalin can reduce the incidence of postoperative chronic neuropathic pain after total hip arthroplasty (THA). This prospective, randomized study compared placebo with pregabalin in the hope that a lower pregabalin dose would improve analgesia without increasing side-effects after THA. METHODS: This study was a prospective randomized blinded study, with a parallel design and an allocation ratio of 1:1 for the treatment groups. The study was approved by the Institutional Review Board in Weifang People's Hospital and written informed consent was obtained from all subjects before enrolment. A total of 120 patients who meet inclusion criteria are randomized to either pregabalin or placebo group. The primary objective of the study was visual analog scale score. As secondary outcomes, opioid consumption measurement, Harris Hip Score, hip range of motion, patient satisfaction, and complications were made at different time points throughout the study for comparison. RESULTS: The null hypothesis of this study was that pregabalin would reduce pain after THA. TRIAL REGISTRATION: This study protocol was registered in Research Registry (researchregistry5669).

Myocardial hypertrophy is improved with berberine treatment via long non-coding RNA MIAT-mediated autophagy.

OBJECTIVES: This study aimed to evaluate berberine (BBR) effects on myocardial hypertrophy (MH) and associated mechanisms. METHODS: BBR effects on MH were evaluated in rats with constriction of abdominal aorta (CAA). qRT-PCR assay was used to measure MH-related genes, long non-coding RNAs (lncRNAs) and autophagy-related genes expressions. Western blot was performed to detect autophagy markers expression. Filamentous actin and phalloidin expressions were detected using immunofluorescence assay. KEY FINDINGS: BBR significantly attenuated CAA-induced MH and cardiomyocyte enlargement. CAA upregulated ß myosin heavy chain and atrial natriuretic peptide expressions in heart tissues, which was attenuated by BBR. BBR suppressed myocardial infarction associated transcript (MIAT) expression in rats with CAA. p62 mRNA expression was upregulated and beclin1 and autophagy related 5 were downregulated in CAA versus control groups. The effects were abolished by BBR. In vitro studies showed that BBR ameliorated angiotensin II-induced MH and attenuated Ang II-induced MIAT expression in H9C2 cells. Expressions of phosphorylated mTOR, phosphorylated AMPK and LC3 were upregulated in H9C2 cells after Ang II stimulation, and the effects were abolished by BBR. CONCLUSIONS: BBR exerted beneficial effects on MH induced by CCA, and the mechanisms were associated with decreased MIAT expression and enhanced autophagy.

BDNF Activates mTOR to Upregulate NR2B Expression in the Rostral Anterior Cingulate Cortex Required for Inflammatory Pain-Related Aversion in Rats.

The mechanistic target of rapamycin (mTOR) has been demonstrated to mediate pain-related aversion induced by formalin in the rostral anterior cingulate cortex (rACC). However, it remains unclear the signaling pathways and regulatory proteins involved. In the rACC, brain-derived neurotrophic factor (BDNF), an activity-dependent neuromodulator, has been shown to play a role in the development and persistence of chronic pain. In this study, we used a rat formalin-induced inflammatory pain model to demonstrate BDNF up-regulation in the rACC. Stimulation with exogenous BDNF up-regulated mTOR, whilst cyclotraxin B (CTX-B), a tropomyosin receptor kinase B (TrkB) antagonist, down-regulated mTOR. Our results suggest BDNF could activate an mTOR signaling pathway. Subsequently, we used formalin-induced conditioned place avoidance (F-CPA) training in rat models to investigate if mTOR activation was required for pain-related aversion. We demonstrated that BDNF/mTOR signaling could activate the NMDA receptor subunit episilon-2 (NR2B), which is required for F-CPA. Our results reveal that BDNF activates mTOR to up-regulate NR2B expression, which is required for inflammatory pain-related aversion in the rACC of rats.

Contribution of BDNF/TrkB signalling in the rACC to the development of pain-related aversion via activation of ERK in rats with spared nerve injury.

The rostral anterior cingulate cortex (rACC) is a key structure in mediating the negative affective component of chronic pain. Brain-derived neurotrophic factor (BDNF) is known to play a critical role in activity-dependent synaptic plasticity, learning and memory. It has been shown that BDNF signalling in the rACC might be involved in spontaneous pain-related aversion, but its underlying mechanism is still largely unknown. To address this question, we measured the mRNA and protein levels of BDNF in the rACC after nerve injury and found that BDNF expression was markedly higher in nerve-injured rats than in controls. Moreover, we found that conditioned place avoidance (CPA), a behavioural phenotype reflecting pain-related aversion, was acquired in rats with partial sciatic nerve transection. However, a local injection of a BDNF-tropomyosin receptor kinase B (TrkB) antagonist into the rACC completely suppressed this process. Importantly, we found that administration of exogenous BDNF into the rACC of intact rats was sufficient to produce CPA, while selectively blocking phosphorylated extracellular signal regulated kinase (p-ERK) with a mitogen-activated protein kinase (MAPK) inhibitor U0126 completely abolished the acquisition of BDNF-induced CPA. In conclusion, we demonstrate, for the first time, that ERK is an important downstream effector of the BDNF/TrkB-mediated signalling pathway in the rACC that contributes to the development of neuropathic pain-related aversion.