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British Journal of Anaesthesia Apr 2019Caudal epidural blockade in children is one of the most widely administered techniques of regional anaesthesia. Recent clinical studies have answered major... (Review)
Review
Caudal epidural blockade in children is one of the most widely administered techniques of regional anaesthesia. Recent clinical studies have answered major pharmacodynamic and pharmacokinetic questions, thus providing the scientific background for safe and effective blocks in daily clinical practice and demonstrating that patient selection can be expanded to range from extreme preterm births up to 50 kg of body weight. This narrative review discusses the main findings in the current literature with regard to patient selection (sub-umbilical vs mid-abdominal indications, contraindications, low-risk patients with spinal anomalies); anatomical considerations (access problems, age and body positioning, palpation for needle insertion); technical considerations (verification of needle position by ultrasound vs landmarks vs 'whoosh' or 'swoosh' testing); training and equipment requirements (learning curve, needle types, risk of tissue spreading); complications and safety (paediatric regional anaesthesia, caudal blocks); local anaesthetics (bupivacaine vs ropivacaine, risk of toxicity in children, management of toxic events); adjuvant drugs (clonidine, dexmedetomidine, opioids, ketamine); volume dosing (dermatomal reach, cranial rebound); caudally accessed lumbar or thoracic anaesthesia (contamination risk, verifying catheter placement); and postoperative pain. Caudal blocks are an efficient way to offer perioperative analgesia for painful sub-umbilical interventions. Performed on sedated children, they enable not only early ambulation, but also periprocedural haemodynamic stability and spontaneous breathing in patient groups at maximum risk of a difficult airway. These are important advantages over general anaesthesia, notably in preterm babies and in children with cardiopulmonary co-morbidities. Compared with other techniques of regional anaesthesia, a case for caudal blocks can still be made.
Topics: Anesthesia, Caudal; Anesthesiology; Anesthetics, Local; Auscultation; Child; Contraindications, Procedure; Education, Medical, Graduate; Epidural Space; Humans; Pain, Postoperative; Palpation; Ultrasonography, Interventional
PubMed: 30857607
DOI: 10.1016/j.bja.2018.11.030 -
Stem Cell Reports Aug 2021Serotonin (5-HT) neurons, the major components of the raphe nuclei, arise from ventral hindbrain progenitors. Based on anatomical location and axonal projection, 5-HT...
Serotonin (5-HT) neurons, the major components of the raphe nuclei, arise from ventral hindbrain progenitors. Based on anatomical location and axonal projection, 5-HT neurons are coarsely divided into rostral and caudal groups. Here, we propose a novel strategy to generate hindbrain 5-HT neurons from human pluripotent stem cells (hPSCs), which involves the formation of ventral-type neural progenitor cells and stimulation of the hindbrain 5-HT neural development. A caudalizing agent, retinoid acid, was used to direct the cells into the hindbrain cell fate. Approximately 30%-40% of hPSCs successfully developed into 5-HT-expressing neurons using our protocol, with the majority acquiring a caudal rhombomere identity (r5-8). We further modified our monolayer differentiation system to generate 5-HT neuron-enriched hindbrain-like organoids. We also suggest downstream applications of our 5-HT monolayer and organoid cultures to study neuronal response to gut microbiota. Our methodology could become a powerful tool for future studies related to 5-HT neurotransmission.
Topics: Animals; Cell Culture Techniques; Cell Differentiation; Cell Line; Humans; Immunohistochemistry; Neural Stem Cells; Neurogenesis; Neurons; Organoids; Pluripotent Stem Cells; Reproducibility of Results; Reverse Transcriptase Polymerase Chain Reaction; Rhombencephalon; Serotonin; Transcriptome; Tretinoin
PubMed: 34242615
DOI: 10.1016/j.stemcr.2021.06.006 -
Brain Communications 2022Of the three largest outputs of the cerebral cortex, two have been extensively studied and mapped. Topographic maps of cortico-thalamic and cortico-striatal functional...
Of the three largest outputs of the cerebral cortex, two have been extensively studied and mapped. Topographic maps of cortico-thalamic and cortico-striatal functional connectivity in humans are well established. However, for the third largest cerebral output, to the pontine nuclei, which connect the cerebrum to the cerebellum, the existence of such an organized connectivity pattern in humans is unknown. Here, using high-resolution functional MRI and a large sample size, we found a topographically organized pattern of functional connectivity between the human cerebral cortex and pons. Our results indicate a rostral-caudal topography; rostral (frontal) cerebral cortex shows connectivity to the rostral pons, and the more caudal cortical areas (i.e. the sensorimotor cortices) show functional connectivity more caudally in the pons, with the occipital lobe connectivity being most caudal. While prefrontal, sensorimotor and occipital cortices have a connectivity to the medial pontine nuclei, posterior parietal cortex and temporal lobe correlate with lateral pontine nuclei. Topography is sufficiently detailed to identify distinct connectivity for leg, trunk, hand and face areas of the motor cortex. These findings reveal the existence of a topographic organization in human cortico-pontine connectivity and provide the topographic map for future studies of cortico-ponto-cerebellum pathway in a variety of disorders.
PubMed: 35265840
DOI: 10.1093/braincomms/fcac047 -
Journal of Integrative Neuroscience Dec 2019The respiratory rhythm is generated by the interaction of oscillators disparately distributed throughout the pons, medulla, and spinal cord. According to the classic... (Review)
Review
The respiratory rhythm is generated by the interaction of oscillators disparately distributed throughout the pons, medulla, and spinal cord. According to the classic model, the interaction amongst preBötzinger complex (preBötzC) spontaneously bursting preinspiratory units and Bötzinger complex (BötzC) expiratory cells generates the principal respiratory rhythm, thence relayed caudally to the pattern generating elements and premotoneurons of the rostral and caudal divisions of the ventral respiratory group and bulbospinal units of the dorsal respiratory group. Rhythm and pattern generating elements in the ventrolateral medulla receive powerful phasic and tonic modulatory inputs from diencephalic structures, midbrain, Kölliker-Fuse, and parabrachial nuclei, retrotrapezoid nucleus, parafacial respiratory group, ventrolateral metencephalon, nucleus tractus solitarius, and brainstem reticular formation, collectively shaping the normal eupneic discharge. Empirical and computational studies have generated models of respiratory rhythmogenesis and pattern formation variously predicated upon pacemaker, network, or hybrid pacemaker network mechanisms to explain oscillatory behavior and regularity. Network mechanisms critically require the integrity and functionality of inhibitory synaptic neurotransmission. The operation and contribution of inhibitory elements in respiratory rhythm generation and pattern formation are well demonstrated empirically and incorporated in computational network and hybrid models of breathing. Fast inhibitory synaptic neurotransmission utilizes GABAAergic and glycinergic mediated activation of receptor linked chloride conductances, generating an inwardly directed flux of chloride ions mediating membrane voltage hyperpolarization and is required to generate eupneic respiratory patterns in vivo and situ. Persistence of rhythmicity in the presence of synaptic antagonism of GABAA and glycine receptor mediated fast inhibitory neurotransmission indicates pacemaker generating mechanisms sufficiently capable of independently generating this behavior in vivo and transected intact preparations maintaining the preBötzC as the most rostrally preserved structure. The role of GABAB receptor mediated neuromodulation in respiratory rhythm generation and pattern formation is comparatively significantly less investigated. GABABergic activation of postsynaptic and presynaptic membrane receptors variably upregulates potassium conductances and downregulates calcium conductances. Respiratory rhythm and pattern are powerfully modulated in vivo, in situ, and in vitro by superfusion or localized microinjections of GABABergic agonists and antagonists, though are typically not abolished by these experimental interventions. Directionality and magnitude of these effects exhibit maturational changes. The relative depolarization of chloride reversal potentials during the early neonatal period, with gradual shifts towards normal hyperpolarizing values during development, suggests GABABergic signaling may mediate the inhibitory neurotransmission necessary to generate triphasic eupnea. We review and discuss the role of spontaneously bursting oscillators and network mechanisms predicating upon fast inhibitory synaptic neurotransmission in contributing to respiratory rhythmogenesis and pattern formation.
Topics: Animals; Brain Stem; Central Pattern Generators; Humans; Periodicity; Receptors, GABA-B; Respiration; Respiratory Center
PubMed: 31912709
DOI: 10.31083/j.jin.2019.04.188 -
Fluids and Barriers of the CNS Oct 2021Cerebrospinal fluid is a clear fluid that occupies the ventricular and subarachnoid spaces within and around the brain and spinal cord. Cerebrospinal fluid is a dynamic... (Review)
Review
Cerebrospinal fluid is a clear fluid that occupies the ventricular and subarachnoid spaces within and around the brain and spinal cord. Cerebrospinal fluid is a dynamic signaling milieu that transports nutrients, waste materials and neuroactive substances that are crucial for the development, homeostasis and functionality of the central nervous system. The mechanisms that enable cerebrospinal fluid to simultaneously exert these homeostatic/dynamic functions are not fully understood. SCO-spondin is a large glycoprotein secreted since the early stages of development into the cerebrospinal fluid. Its domain architecture resembles a combination of a matricellular protein and the ligand-binding region of LDL receptor family. The matricellular proteins are a group of extracellular proteins with the capacity to interact with different molecules, such as growth factors, cytokines and cellular receptors; enabling the integration of information to modulate various physiological and pathological processes. In the same way, the LDL receptor family interacts with many ligands, including β-amyloid peptide and different growth factors. The domains similarity suggests that SCO-spondin is a matricellular protein enabled to bind, modulate, and transport different cerebrospinal fluid molecules. SCO-spondin can be found soluble or polymerized into a dynamic threadlike structure called the Reissner fiber, which extends from the diencephalon to the caudal tip of the spinal cord. Reissner fiber continuously moves caudally as new SCO-spondin molecules are added at the cephalic end and are disaggregated at the caudal end. This movement, like a conveyor belt, allows the transport of the bound molecules, thereby increasing their lifespan and action radius. The binding of SCO-spondin to some relevant molecules has already been reported; however, in this review we suggest more than 30 possible binding partners, including peptide β-amyloid and several growth factors. This new perspective characterizes SCO-spondin as a regulator of cerebrospinal fluid activity, explaining its high evolutionary conservation, its apparent multifunctionality, and the lethality or severe malformations, such as hydrocephalus and curved body axis, of knockout embryos. Understanding the regulation and identifying binding partners of SCO-spondin are crucial for better comprehension of cerebrospinal fluid physiology.
Topics: Animals; Brain; CCN Intercellular Signaling Proteins; Cell Adhesion Molecules, Neuronal; Cerebrospinal Fluid
PubMed: 34600566
DOI: 10.1186/s12987-021-00277-w -
Medicine Jul 2020To evaluate the efficacy and safety of caudal dexmedetomidine in pediatric caudal anesthesia (CA). (Meta-Analysis)
Meta-Analysis
OBJECTIVES
To evaluate the efficacy and safety of caudal dexmedetomidine in pediatric caudal anesthesia (CA).
METHODS
We searched PubMed, Embased, and Cochrane Library (from inception to June 2019) for eligible studies. The primary outcomes were the time to first analgesia, time of postoperative eye opening, intraoperative endtidal sevoflurane concentration, and postoperative sedation score. We calculated pooled risk ratios (RR) and 95% CIs using random- or fixed-effects models.
RESULTS
Thirteen trials involving 793 patients were found. Meta-analysis showed that the time to first rescue pain medication and the time from the end of anesthesia to eye opening in the CA+dexmedetomidine group were significantly longer than in the CA group (P < .00001). The intraoperative end-tidal sevoflurane concentration in the CA+dexmedetomidine group was significantly decreased (P < .00001). Dexmedetomidine appeared to increase the rate of bradycardia in the CA+dexmedetomidine group (P = .04). Additionally, the sedation score in the CA+ dexmedetomidine group was significantly higher at 2 hours after the operation compared with the CA group (P < .00001 at 2 hours).
CONCLUSIONS
Caudally administered dexmedetomidine is a good alternative for prolonging postoperative analgesia with less pain, decreased intraoperative end-tidal sevoflurane concentration, and full postoperative sedation.
Topics: Anesthesia, Caudal; Child; Dexmedetomidine; Humans; Hypnotics and Sedatives; Pain, Postoperative; Randomized Controlled Trials as Topic
PubMed: 32756133
DOI: 10.1097/MD.0000000000021397