Astrocytes modulate a specific paraventricular thalamus-prefrontal cortex projection to enhance consciousness recovery from anesthesia.

Current anesthetic theory is mostly based on neurons and/or neuronal circuits. A role for astrocytes also has been shown in promoting recovery from volatile anesthesia, while the exact modulatory mechanism and/or the molecular target in astrocytes is still unknown. In this study, by animal models in male mice and electrophysiological recordings in vivo and in vitro, we found that activating astrocytes of paraventricular thalamus (PVT) and/or knocking down PVT astrocytic Kir4.1 promoted the consciousness recovery from sevoflurane anesthesia. Single-cell RNA sequencing of PVT reveals two distinct cellular subtypes of glutamatergic neurons: PVT GRM and PVT ChAT neurons. Patch-clamp recording results proved astrocytic Kir4.1-mediated modulation of sevoflurane on PVT mainly worked on PVT ChAT neurons, which projected mainly to the mPFC. In summary, our findings support the novel conception that there is a specific PVT-prefrontal cortex projection involved in consciousness recovery from sevoflurane anesthesia, which mediated by the inhibition of sevoflurane on PVT astrocytic Kir4.1 conductance.Significance Statement How volatile anesthetics work is not fully understood. Here, we demonstrate that the commonly used volatile anesthetic sevoflurane can inhibit astrocytic Kir4.1 conductance in PVT, which enhances neuronal firing of PVT neurons. Additionally, by single-cell sequencing, cholinergic neurons in the PVT (PVT ChAT ) are the neuronal substrates for astrocytic modulation in volatile anesthesia, which directly project to prefrontal cortex. Behaviorally, the modulation of astrocytes on PVT ChAT promotes electroencephalogram (EEG) transition of prefrontal cortex; and then accelerates emergence from sevoflurane anesthesia. In summary, this study is the first to identify that astrocytic Kir4.1 in wakeful nuclei is involved in consciousness recovery from volatile anesthetics, as well as the subcellular mechanism.

Spatial transcriptomics combined with single-nucleus RNA sequencing reveals glial cell heterogeneity in the human spinal cord.

ABSTRACT: Glial cells play crucial roles in regulating physiological and pathological functions, including sensation, the response to infection and acute injury, and chronic neurodegenerative disorders. Glial cells include astrocytes, microglia, and oligodendrocytes in the central nervous system, and satellite glial cells and Schwann cells in the peripheral nervous system. Despite the greater understanding of glial cell types and functional heterogeneity achieved through single-cell and single-nucleus RNA sequencing in animal models, few studies have investigated the transcriptomic profiles of glial cells in the human spinal cord. Here, we used high-throughput single-nucleus RNA sequencing and spatial transcriptomics to map the cellular and molecular heterogeneity of astrocytes, microglia, and oligodendrocytes in the human spinal cord. To explore the conservation and divergence across species, we compared these findings with those from mice. In the human spinal cord, astrocytes, microglia, and oligodendrocytes were each divided into six distinct transcriptomic subclusters. In the mouse spinal cord, astrocytes, microglia, and oligodendrocytes were divided into five, four, and five distinct transcriptomic subclusters, respectively.The comparative results revealed substantial heterogeneity in all glial cell types between humans and mice. Additionally, we detected sex differences in gene expression in human spinal cord glial cells. Specifically, in all astrocyte subtypes, the levels of NEAT1 and CHI3L1 were higher in males than in females, whereas the levels of CST3 were lower in males than in females. In all microglial subtypes, all differentially expressed genes were located on the sex chromosomes. In addition to sex-specific gene differences, the levels of MT-ND4, MT2A, MT-ATP6, MT-CO3, MT-ND2, MT-ND3, and MT-CO2 in all spinal cord oligodendrocyte subtypes were higher in females than in males. Collectively, the present dataset extensively characterizes glial cell heterogeneity and offers a valuable resource for exploring the cellular basis of spinal cord-related illnesses, including chronic pain, amyotrophic lateral sclerosis, and multiple sclerosis.

Distinct Neural Mechanisms Between Anesthesia Induction and Emergence: A Narrative Review.

Anesthesia induction and emergence are critical periods for perioperative safety in the clinic. Traditionally, the emergence from general anesthesia has been recognized as a simple inverse process of induction resulting from the elimination of general anesthetics from the central nervous system. However, accumulated evidence has indicated that anesthesia induction and emergence are not mirror-image processes because of the occurrence of hysteresis/neural inertia in both animals and humans. An increasing number of studies have highlighted the critical role of orexinergic neurons and their involved circuits in the selective regulation of emergence but not the induction of general anesthesia. Moreover, additional brain regions have also been implicated in distinct neural mechanisms for anesthesia induction and emergence, which extends the concept that anesthetic induction and emergence are not antiparallel processes. Here, we reviewed the current literature and summarized the evidence regarding the differential mechanism of neural modulation in anesthesia induction and emergence, which will facilitate the understanding of the underlying neural mechanism for emergence from general anesthesia.

Sodium Leak Channel in Glutamatergic Neurons of the Lateral Parabrachial Nucleus Helps to Maintain Respiratory Frequency Under Sevoflurane Anesthesia.

The lateral parabrachial nucleus (PBL) is implicated in the regulation of respiratory activity. Sodium leak channel (NALCN) mutations disrupt the respiratory rhythm and influence anesthetic sensitivity in both rodents and humans. Here, we investigated whether the NALCN in PBL glutamatergic neurons maintains respiratory function under general anesthesia. Our results showed that chemogenetic activation of PBL glutamatergic neurons increased the respiratory frequency (RF) in mice; whereas chemogenetic inhibition suppressed RF. NALCN knockdown in PBL glutamatergic neurons but not GABAergic neurons significantly reduced RF under physiological conditions and caused more respiratory suppression under sevoflurane anesthesia. NALCN knockdown in PBL glutamatergic neurons did not further exacerbate the respiratory suppression induced by propofol or morphine. Under sevoflurane anesthesia, painful stimuli rapidly increased the RF, which was not affected by NALCN knockdown in PBL glutamatergic neurons. This study suggested that the NALCN is a key ion channel in PBL glutamatergic neurons that maintains respiratory frequency under volatile anesthetic sevoflurane but not intravenous anesthetic propofol.

Effects of Bright Light Therapy on Agitation Among Older Adults Living with Dementia in Macao: A Pilot Study.

A randomized controlled trial was conducted to examine the effects of bright light therapy on agitation in older adults with dementia in Macao. This study involved 31 participants: 10 in the outdoor light treatment group, 11 in the indoor light-box treatment group, and 10 in the control group. Significant reductions in agitation were observed in the two treatment groups over four weeks compared to the control group. However, no statistical difference in cognitive function between experimental and control groups was found. This study supports the use of bright light therapy to reduce agitation in older people with dementia.

Optimal approach for ultrasound-guided transversus abdominis plane (TAP) blocks for abdominal surgeries: a protocol for systematic review and meta-analysis.

INTRODUCTION: Transversus abdominis plane (TAP) blocks are commonly used for postoperative analgesia after various abdominal surgeries. There are several different approaches for performing TAP blocks, mainly including posterior, lateral and subcostal approaches. An increasing number of randomised controlled trials (RCTs) have compared the analgesic effects of different TAP block approaches, but the results have not been consistent. This protocol aims to determine the optimal approach of ultrasound-guided TAP blocks for postoperative analgesia after abdominal surgery. METHODS AND ANALYSIS: Four databases, including Web of Science, PubMed, EMBASE and the Cochrane Library will be systematically searched to identify RCTs that compared the analgesic effects of different ultrasound-guided TAP block approaches. The search interval will range from the inception of the databases to 30 July 2024. The postoperative opioid consumption over 24 hours will be defined as the primary outcome. The secondary outcomes will include the analgesia duration, postoperative pain scores at rest and during movement at different timepoints and the incidence of adverse effects. All the statistical analyses will be conducted using RevMan V.5.4. The quality of evidence will be evaluated by the Grading of Recommendations Assessment, Development and Evaluation approach. ETHICS AND DISSEMINATION: Ethical approval will not be needed. The results will be submitted to one peer-reviewed journal when completed. PROSPERO REGISTRATION NUMBER: CRD42024510141.

Effects of flipped classroom teaching in anaesthesiology residents: a protocol for systematic review and meta-analysis.

INTRODUCTION: The flipped classroom teaching model is widely used in medical education and is indicated to be better than traditional lecture approaches in many medical specialties. Emerging studies have evaluated the effects of the flipped classroom teaching model on anaesthesiology residents. This protocol aims to perform a systematic review and meta-analysis to determine whether the flipped classroom teaching model is superior to traditional teaching methods for anaesthesiology residents. METHODS AND ANALYSIS: Seven databases, including PubMed, Web of Science, EMBASE, the Cochrane Library, the China National Knowledge Infrastructure, Wanfang Data and the VIP database, will be systematically searched from their inception to 1 June 2024. Randomised controlled trials that compared the effects of flipped classrooms versus traditional teaching methods in anaesthesiology residents will be included. The primary outcome will be the theoretical knowledge score. The secondary outcomes will include skill scores and the proportion of anaesthesiology residents who preferred the flipped classroom model. RevMan V.5.4 software will be used to perform the statistical analysis. The Grading of Recommendation, Assessment, Development and Evaluation approach will assess the quality of evidence. ETHICS AND DISSEMINATION: Ethical approval is not applicable to this protocol. The results of this study will be submitted to a peer-reviewed journal. PROSPERO REGISTRATION NUMBER: CRD42024497935.

Activity of the Sodium Leak Channel Maintains the Excitability of Paraventricular Thalamus Glutamatergic Neurons to Resist Anesthetic Effects of Sevoflurane in Mice.

BACKGROUND: Stimulation of the paraventricular thalamus has been found to enhance anesthesia recovery; however, the underlying molecular mechanism by which general anesthetics modulate paraventricular thalamus is unclear. This study aimed to test the hypothesis that the sodium leak channel (NALCN) maintains neuronal activity in the paraventricular thalamus to resist anesthetic effects of sevoflurane in mice. METHODS: Chemogenetic and optogenetic manipulations, in vivo multiple-channel recordings, and electroencephalogram recordings were used to investigate the role of paraventricular thalamus neuronal activity in sevoflurane anesthesia. Virus-mediated knockdown and/or overexpression was applied to determine how NALCN influenced excitability of paraventricular thalamus glutamatergic neurons under sevoflurane. Viral tracers and local field potentials were used to explore the downstream pathway. RESULTS: Single neuronal spikes in the paraventricular thalamus were suppressed by sevoflurane anesthesia and recovered during emergence. Optogenetic activation of paraventricular thalamus glutamatergic neurons shortened the emergence period from sevoflurane anesthesia, while chemogenetic inhibition had the opposite effect. Knockdown of the NALCN in the paraventricular thalamus delayed the emergence from sevoflurane anesthesia (recovery time: from 24 ± 14 to 64 ± 19 s, P < 0.001; concentration for recovery of the righting reflex: from 1.13% ± 0.10% to 0.97% ± 0.13%, P < 0.01). As expected, the overexpression of the NALCN in the paraventricular thalamus produced the opposite effects. At the circuit level, knockdown of the NALCN in the paraventricular thalamus decreased the neuronal activity of the nucleus accumbens, as indicated by the local field potential and decreased single neuronal spikes in the nucleus accumbens. Additionally, the effects of NALCN knockdown in the paraventricular thalamus on sevoflurane actions were reversed by optical stimulation of the nucleus accumbens. CONCLUSIONS: Activity of the NALCN maintains the excitability of paraventricular thalamus glutamatergic neurons to resist the anesthetic effects of sevoflurane in mice.

The relationship between marital status and cognitive impairment in Chinese older adults: the multiple mediating effects of social support and depression.

BACKGROUND: Marital status is a potentially essential factor for cognitive impairment. Relevant research examining the potential pathways through which the marital status of spouseless older people is associated with cognitive impairment needs to be more adequate. Therefore, this study aims to investigate the serial mediating effects of various forms of social support and depression between marital status and cognitive impairment in older Chinese people. METHODS: This study involved a secondary analysis of data from the 2014-2018 wave of the Chinese Longitudinal Healthy Longevity Survey (CLHLS), with a total of 2,647 Chinese older adults and 53.6% being males. Mediation analysis using the SPSS process macro was conducted. RESULTS: The results indicated that marital status was significantly predictive of cognitive impairment among older people, and those with a spouse exhibited higher cognitive functioning. Informal social support and depression were found to play partial mediating roles in the association between marital status and cognitive impairment. The findings also revealed that marital status was unrelated to formal social support, and no association between formal social support and cognitive impairment was found. CONCLUSIONS: The study findings highlight the need for social service providers to design programs for promoting connections associated with informal support to reduce their risk of depression and cognitive impairment and for policymakers to develop effective formal social support systems for older people without spouses. This study indicated that older people could regain the benefits of marriage to lower the risk of depression and improve their mental health.

Comparison of the effects of ultrasound-guided quadratus lumborum block and erector spinae plane block on postoperative pain in abdominal surgeries: a protocol for systematic review and meta-analysis.

INTRODUCTION: Ultrasound-guided quadratus lumborum block and erector spinae plane block are widely used for postoperative analgesia in adult patients undergoing abdominal surgeries. This protocol aims to compare the analgesic effects between ultrasound-guided quadratus lumborum block and erector spinae plane block on postoperative pain in abdominal surgeries. METHODS AND ANALYSIS: Four databases, including PubMed, EMBASE, Web of Science and the Cochrane Central Register of Controlled Trials (CENTRAL), will be searched. Randomised controlled trials that compared the analgesic effects between ultrasound-guided quadratus lumborum block and erector spinae plane block on postoperative pain in adult patients will be identified. The primary outcomes are time to the first analgesic request and postoperative analgesic consumption over 24 hours. Secondary outcomes will include postoperative pain scores and the incidence of side effects. RevMan V.5.3 software will be used for data processing and statistical analysis. The Grading of Recommendation, Assessment, Development and Evaluation approach will be used to assess the evidence quality of outcomes. ETHICS AND DISSEMINATION: Ethical approval is not required for this study. Results of this present study will be submitted to a peer-reviewed journal. PROSPERO REGISTRATION NUMBER: CRD42023445802.

Spatial transcriptomics and single-nucleus RNA sequencing reveal a transcriptomic atlas of adult human spinal cord.

Despite the recognized importance of the spinal cord in sensory processing, motor behaviors, and neural diseases, the underlying organization of neuronal clusters and their spatial location remain elusive. Recently, several studies have attempted to define the neuronal types and functional heterogeneity in the spinal cord using single-cell or single-nucleus RNA sequencing in animal models or developing humans. However, molecular evidence of cellular heterogeneity in the adult human spinal cord is limited. Here, we classified spinal cord neurons into 21 subclusters and determined their distribution from nine human donors using single-nucleus RNA sequencing and spatial transcriptomics. Moreover, we compared the human findings with previously published single-nucleus data of the adult mouse spinal cord, which revealed an overall similarity in the neuronal composition of the spinal cord between the two species while simultaneously highlighting some degree of heterogeneity. Additionally, we examined the sex differences in the spinal neuronal subclusters. Several genes, such as SCN10A and HCN1, showed sex differences in motor neurons. Finally, we classified human dorsal root ganglia (DRG) neurons using spatial transcriptomics and explored the putative interactions between DRG and spinal cord neuronal subclusters. In summary, these results illustrate the complexity and diversity of spinal neurons in humans and provide an important resource for future research to explore the molecular mechanisms underlying spinal cord physiology and diseases.

γ-Aminobutyric Acid-Ergic Development Contributes to the Enhancement of Electroencephalogram Slow-Delta Oscillations Under Volatile Anesthesia in Neonatal Rats.

BACKGROUND: General anesthetics (eg, propofol and volatile anesthetics) enhance the slow-delta oscillations of the cortical electroencephalogram (EEG), which partly results from the enhancement of (γ-aminobutyric acid [GABA]) γ-aminobutyric acid-ergic (GABAergic) transmission. There is a GABAergic excitatory-inhibitory shift during postnatal development. Whether general anesthetics can enhance slow-delta oscillations in the immature brain has not yet been unequivocally determined. METHODS: Perforated patch-clamp recording was used to confirm the reversal potential of GABAergic currents throughout GABAergic development in acute brain slices of neonatal rats. The power density of the electrocorticogram and the minimum alveolar concentrations (MAC) of isoflurane and/or sevoflurane were measured in P4-P21 rats. Then, the effects of bumetanide, an inhibitor of the Na + -K + -2Cl - cotransporter (NKCC1) and K + -Cl - cotransporter (KCC2) knockdown on the potency of volatile anesthetics and the power density of the EEG were determined in vivo. RESULTS: Reversal potential of GABAergic currents were gradually hyperpolarized from P4 to P21 in cortical pyramidal neurons. Bumetanide enhanced the hypnotic effects of volatile anesthetics at P5 (for MAC LORR , isoflurane: 0.63% ± 0.07% vs 0.81% ± 0.05%, 95% confidence interval [CI], -0.257 to -0.103, P < .001; sevoflurane: 1.46% ± 0.12% vs 1.66% ± 0.09%, 95% CI, -0.319 to -0.081, P < .001); while knockdown of KCC2 weakened their hypnotic effects at P21 in rats (for MAC LORR , isoflurane: 0.58% ± 0.05% to 0.77% ± 0.20%, 95% CI, 0.013-0.357, P = .003; sevoflurane: 1.17% ± 0.04% to 1.33% ± 0.04%, 95% CI, 0.078-0.244, P < .001). For cortical EEG, slow-delta oscillations were the predominant components of the EEG spectrum in neonatal rats. Isoflurane and/or sevoflurane suppressed the power density of slow-delta oscillations rather than enhancement of it until GABAergic maturity. Enhancement of slow-delta oscillations under volatile anesthetics was simulated by preinjection of bumetanide at P5 (isoflurane: slow-delta changed ratio from -0.31 ± 0.22 to 1.57 ± 1.15, 95% CI, 0.67-3.08, P = .007; sevoflurane: slow-delta changed ratio from -0.46 ± 0.25 to 0.95 ± 0.97, 95% CI, 0.38-2.45, P = .014); and suppressed by KCC2-siRNA at P21 (isoflurane: slow-delta changed ratio from 16.13 ± 5.69 to 3.98 ± 2.35, 95% CI, -18.50 to -5.80, P = .002; sevoflurane: slow-delta changed ratio from 0.13 ± 2.82 to 3.23 ± 2.49, 95% CI, 3.02-10.79, P = .003). CONCLUSIONS: Enhancement of cortical EEG slow-delta oscillations by volatile anesthetics may require mature GABAergic inhibitory transmission during neonatal development.

The Modulation by Anesthetics and Analgesics of Respiratory Rhythm in the Nervous System.

Rhythmic eupneic breathing in mammals depends on the coordinated activities of the neural system that sends cranial and spinal motor outputs to respiratory muscles. These outputs modulate lung ventilation and adjust respiratory airflow, which depends on the upper airway patency and ventilatory musculature. Anesthetics are widely used in clinical practice worldwide. In addition to clinically necessary pharmacological effects, respiratory depression is a critical side effect induced by most general anesthetics. Therefore, understanding how general anesthetics modulate the respiratory system is important for the development of safer general anesthetics. Currently used volatile anesthetics and most intravenous anesthetics induce inhibitory effects on respiratory outputs. Various general anesthetics produce differential effects on respiratory characteristics, including the respiratory rate, tidal volume, airway resistance, and ventilatory response. At the cellular and molecular levels, the mechanisms underlying anesthetic-induced breathing depression mainly include modulation of synaptic transmission of ligand-gated ionotropic receptors (e.g., γ-aminobutyric acid, N-methyl-D-aspartate, and nicotinic acetylcholine receptors) and ion channels (e.g., voltage-gated sodium, calcium, and potassium channels, two-pore domain potassium channels, and sodium leak channels), which affect neuronal firing in brainstem respiratory and peripheral chemoreceptor areas. The present review comprehensively summarizes the modulation of the respiratory system by clinically used general anesthetics, including the effects at the molecular, cellular, anatomic, and behavioral levels. Specifically, analgesics, such as opioids, which cause respiratory depression and the "opioid crisis", are discussed. Finally, underlying strategies of respiratory stimulation that target general anesthetics and/or analgesics are summarized.

Optimal concentration of ropivacaine for peripheral nerve blocks in adult patients: a protocol for systematic review and meta-analysis.

INTRODUCTION: Ropivacaine is the most widely used local anaesthetic for peripheral nerve blocks (PNBs). The effects of various concentrations of ropivacaine in PNB have been investigated and compared by many randomised controlled trials (RCTs). This protocol aims to identify the optimal concentration of ropivacaine for PNB in adult patients. METHODS AND ANALYSIS: PubMed, EMBASE, the Cochrane library and Web of Science will be searched from their inception to 10 July 2023. RCTs that compare the analgesic effects of different concentrations of ropivacaine for PNB will be included. Retrospective studies, meta-analyses, reviews, case reports, letters, conference abstracts and paediatric studies will be excluded. The duration of analgesia will be named as the primary outcome. Secondary outcomes will include the onset time of motor and sensory blockade, postoperative pain scores, analgesic requirements over 24 hours and the incidence of adverse effects. The study selection, data extraction and quality assessment will be performed by two independent reviewers. Data processing and analysis will be performed by RevMan 5.4. The quality of the evidence will be assessed by the Grading of Recommendations Assessment, Development and Evaluation approach. ETHICS AND DISSEMINATION: Ethical approval is not applicable. The results of this study will be submitted to peer-reviewed journals. PROSPERO REGISTRATION NUMBER: CRD42023406362.

Optimal concentration of ropivacaine for brachial plexus blocks in adult patients undergoing upper limb surgeries: a systematic review and meta-analysis.

Aim of the Study: Brachial plexus block (BPB) is widely used for patients undergoing upper limb surgeries. Ropivacaine is the most commonly used local anesthetic for BPB. This study aimed to identify the optimal ropivacaine concentration for BPB in adult patients undergoing upper limb surgeries. Materials and Methods: PubMed, Embase, the Cochrane Library, and Web of Science were searched to identify randomized controlled trials (RCTs) that compared the effects of different concentrations of ropivacaine for BPB in adult patients undergoing upper limb surgeries. The primary outcomes were the onset time of sensory and motor block. RevMan 5.4 software was used for analysis. The GRADE approach was used to assess evidence quality. Results: Nine studies involving 504 patients were included. Compared to 0.5% ropivacaine, 0.75% ropivacaine shortened the onset time of sensory (WMD, -2.54; 95% CI; -4.84 to -0.24; <0.0001, moderate quality of evidence) and motor blockade (WMD, -2.46; 95% CI, -4.26 to -0.66; p = 0.01; moderate quality of evidence). However, 0.5% and 0.75% ropivacaine provided similar duration time of sensory (WMD, -0.07; 95% CI, -0.88 to 0.74; p = 0.81; high quality of evidence) and motor blockade (WMD, -0.24; 95% CI, -1.12 to 0.65; p = 0.55; high quality of evidence), as well as time to first request for oral analgesia (WMD, -1.57; 95% CI, -3.14 to 0.01; p = 0.5; moderate quality of evidence). Conclusion: Moderate-quality evidence suggested that, in terms of the onset time of sensory and motor blockade, 0.75% ropivacaine is a preferred concentration for BPB in upper limb surgeries. Systematic Review Registration: identifier CRD42023392145.

Sodium Leak Channel in Glutamatergic Neurons of the Lateral Parabrachial Nucleus Modulates Inflammatory Pain in Mice.

Elevated excitability of glutamatergic neurons in the lateral parabrachial nucleus (PBL) is associated with the pathogenesis of inflammatory pain, but the underlying molecular mechanisms are not fully understood. Sodium leak channel (NALCN) is widely expressed in the central nervous system and regulates neuronal excitability. In this study, chemogenetic manipulation was used to explore the association between the activity of PBL glutamatergic neurons and pain thresholds. Complete Freund's adjuvant (CFA) was used to construct an inflammatory pain model in mice. Pain behaviour was tested using von Frey filaments and Hargreaves tests. Local field potential (LFP) was used to record the activity of PBL glutamatergic neurons. Gene knockdown techniques were used to investigate the role of NALCN in inflammatory pain. We further explored the downstream projections of PBL using cis-trans-synaptic tracer virus. The results showed that chemogenetic inhibition of PBL glutamatergic neurons increased pain thresholds in mice, whereas chemogenetic activation produced the opposite results. CFA plantar modelling increased the number of C-Fos protein and NALCN expression in PBL glutamatergic neurons. Knockdown of NALCN in PBL glutamatergic neurons alleviated CFA-induced pain. CFA injection induced C-Fos protein expression in central nucleus amygdala (CeA) neurons, which was suppressed by NALCN knockdown in PBL glutamatergic neurons. Therefore, elevated expression of NALCN in PBL glutamatergic neurons contributes to the development of inflammatory pain via PBL-CeA projections.

Single-cell transcriptomic profiling of dorsal root ganglion: an overview.

The somatosensory neurons in the dorsal root ganglion (DRG) are responsible to detect peripheral physical and noxious stimuli, and then transmit these inputs into the central nervous system. DRG neurons are composed of various subpopulations, which are suggested to respond to different stimuli, such as mechanical, thermal, and cold perception. For a long time, DRG neurons were classified based on anatomical criteria. Recently, single-cell (scRNA-seq) and single-nucleus RNA-sequencing (snRNA-seq) has advanced our understanding of the composition and functional heterogeneity of both human and rodent DRG neurons at single-cell resolution. In this review, we summarized the current literature regarding single-cell transcriptomic profiling of DRG to provide an integral understanding in the molecular transcriptomes, cell types, and functional annotations of DRG neurons in humans and rodents.

Optimal dose of perineural dexamethasone for the prolongation of analgesia for peripheral nerve blocks: protocol for a systematic review and meta-analysis.

INTRODUCTION: Perineural use of dexamethasone is demonstrated to extend the analgesia duration of peripheral nerve blocks (PNB), but its optimal dose remains unclear. This systematic review and meta-analysis aims to determine the optimal dose of perineural dexamethasone in the prolongation of analgesia for PNB. METHODS AND ANALYSIS: PubMed, EMBASE, the Cochrane Central Register of Controlled Trials and Web of Science will be searched from their inception to 1 March 2023. Language will be restricted to English. Randomised controlled trials that compared the efficacy and safety of different doses of perineural dexamethasone for PNB in adult patients will be included. Retrospective studies, reviews, meta-analyses, case reports, conference abstracts, comments and studies regarding paediatric surgeries will be excluded. The duration of analgesia will be defined as the primary outcome. Secondary outcomes will include pain scores, the total analgesic requirement over 48 hours and the incidence of adverse effects. Two reviewers will independently perform the study selection, data extraction and quality assessment. RevMan V.5.3 software will be used for data analysis. The quality of evidence will be assessed using the Grading of Recommendation, Assessment, Development and Evaluation (GRADE) approach. ETHICS AND DISSEMINATION: No ethical approval is required. The results of this study will be submitted to peer-reviewed journals. PROSPERO REGISTRATION NUMBER: CRD42022385672.

Metabolomics analysis in rat hearts with ischemia/reperfusion injury after diazoxide postconditioning.

Background: Diazoxide is a selective mitochondrial-sensitive potassium channel opening agent that has a definite effect on reducing myocardial ischemia/reperfusion injury (MIRI). However, the exact effects of diazoxide postconditioning on the myocardial metabolome remain unclear, which might contribute to the cardioprotective effects of diazoxide postconditioning. Methods: Rat hearts subjected to Langendorff perfusion were randomly assigned to the normal (Nor) group, ischemia/reperfusion (I/R) group, diazoxide (DZ) group and 5-hydroxydecanoic acid + diazoxide (5-HD + DZ) group. The heart rate (HR), left ventricular developed pressure (LVDP), left ventricular end-diastolic pressure (LVEDP), and maximum left ventricular pressure (+dp/dtmax) were recorded. The mitochondrial Flameng scores were analysed according to the ultrastructure of the ventricular myocardial tissue in the electron microscopy images. Rat hearts of each group were used to investigate the possible metabolic changes relevant to MIRI and diazoxide postconditioning. Results: The cardiac function indices in the Nor group were better than those in the other groups at the end point of reperfusion, and the HR, LVDP and +dp/dtmax of the Nor group at T2 were significantly higher than those of the other groups. Diazoxide postconditioning significantly improved cardiac function after ischaemic injury, and the HR, LVDP and +dp/dtmax of the DZ group at T2 were significantly higher than those of the I/R group, which could be abolished by 5-HD. The HR, LVDP and +dp/dtmax of the 5-HD + DZ group at T2 were significantly lower than those of the DZ group. The myocardial tissue in the Nor group was mostly intact, while it exhibited considerable damage in the I/R group. The ultrastructural integrity of the myocardium in the DZ group was higher than that in the I/R and 5-HD + DZ groups. The mitochondrial Flameng score in the Nor group was lower than that in the I/R, DZ and 5-HD + DZ groups. The mitochondrial Flameng score in the DZ group was lower than that in the I/R and 5-HD + DZ groups. Five metabolites, namely, L-glutamic acid, L-threonine, citric acid, succinate, and nicotinic acid, were suggested to be associated with the protective effects of diazoxide postconditioning on MIRI. Conclusion: Diazoxide postconditioning may improve MIRI via certain metabolic changes. This study provides resource data for future studies on metabolism relevant to diazoxide postconditioning and MIRI.