Dexmedetomidine mitigates sevoflurane-induced cell cycle arrest in hippocampus

Abstract

Background

Epidemiologic studies suggest the possibility of a modestly elevated risk of adverse neurodevelopmental outcomes in children exposed to anesthesia during early childhood. Sevoflurane is widely used in pediatric anesthetic practice because of its rapid induction and lower pungency. However, it is reported that sevoflurane leads to the long-term cognitive impairment. Some evidence revealed that the selective α2-adrenoreceptor agonist dexmedetomidine (DEX) exerts neuroprotective effects in various brain injury models of animals. But the role of DEX on sevoflurane-induced neuro-damage remains elusive.

Materials and methods

In our study, we isolated the hippocampal neuron cells from newborn neonatal rats and verified the purity of neurons by immunocytochemistry. We employed the flow cytometry and western blot to examine the effect of sevoflurane, DEX and α2-adrenergic receptor antagonist yohimbine on cell cycle distribution.

Results

Immunocytochemistry results showed the purity of neurons > 94%, which provided a good model for neural pharmacology experiments. The exposure of sevoflurane-induced cell cycle arrest at S phase and suppressed the expression of brain-derived neurotrophic factor (BDNF) and tyrosine kinase B (TrkB). The addition of DEX suppressed sevoflurane-induced cell cycle arrest and the inhibitory of BDNF and TrkB expression. But the function of DEX was partly blocked by a α2 adrenergic receptor blocker yohimbine.

Conclusion

Sevoflurane suppressed neuron cell proliferation via inhibiting the expression of BDNF and TrkB, and DEX relieved the neurotoxicity induced by sevoflurane via α2 adrenergic receptor. These findings provided new evidence that DEX exerted as a neuroprotective strategy in sevoflurane-induced neuro-damage, and provided new basis for the clinical application of DEX.

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The tendinous septum of the semispinalis capitis muscle spatially separates the dorsal ramus between C3 and C4

Abstract

Local anesthetic injection into the medial head of the semispinalis capitis muscle can anesthetize the greater occipital nerve (GON) and third occipital nerve (TON) simultaneously (greater and third occipital nerve block: GTO block). Alternatively, inter-semispinal plane (ISP) block can anesthetize the dorsal rami of the cervical spinal nerves from C4 to T4. The GON, TON, and the dorsal rami of the inferior level cannot be blocked with a single injection. To elucidate this phenomenon from an anatomical standpoint, we performed an ISP block either alone or with a GTO block using water-based acrylic dye in three thiel-embalmed cadavers. Both dyes were clearly separated by the tendinous septum running obliquely inside the semispinalis capitis muscle (SCA). The tendinous septum of the SCA may have a relatively strong connection with the dorsal edge of the semispinalis cervicis muscle, and this structure may stem the injectate spread. Therefore, the GON and TON, running through the medial head of the SCA, and the dorsal rami of the inferior level are spatially separated by the tendinous septum, and cannot be blocked with a single injection.

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Role of allergen-specific T-follicular helper cells in immunotherapy

Purpose of review The discovery of novel T-cell subsets including follicular helper T (Tfh) cells has broadened our knowledge on the complex immune networks in allergic diseases. This review summarizes the evidence for Tfh cells in controlling immune responses to allergens with a particular focus on immunoglobulin E (IgE) production and discusses the implication of such regulation in allergen-specific immunotherapy. Recent findings Tfh cells support the production of IgE in animal models for allergic diseases. Among Tfh cells, the type 2 subset (Tfh2) is considered as the major player that secretes IL-4 and promotes the isotype switching to IgE. In human inflammatory airway diseases, including allergic rhinitis, asthma, and nasal polyps, the increased frequencies of circulating or tissue Tfh2 cells have been reported. Notably, the frequencies of Dermatophagoides pteronyssinus group 1 (Der p 1)-specific IL-4+ Tfh cells in blood positively correlated with serum Der p-specific IgE levels in allergic rhinitis patients. After allergen immunotherapy (AIT), Der p 1-specific IL-4+ Tfh cells declined in allergic rhinitis patients, which associated with the remission of clinical symptoms. Summary Allergen-specific IL-4+ Tfh cells contribute to the production of allergen-specific IgE and correlate with clinical efficacy of AIT in allergic rhinitis patients, which suggest allergen-specific Tfh cells as a promising therapeutic target and biomarker for AIT in allergic rhinitis. Correspondence to Zheng Liu, MD, PhD, Department of Otolaryngology-Head and Neck Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1095 Jiefang Avenue, Wuhan 430030, People's Republic of China. E-mail: zhengliuent@hotmail.com Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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Echo-guided invasive pain therapy: indications and limitations

Purpose of review The purposes of this review are to summarize the advantages and limitations of ultrasound-guided pain interventions, and to illustrate those interventions with peripheral, axial and musculoskeletal pain procedures. Recent findings With the capability of locating the interfascial plane, ultrasonography has led to the emergence of a series of plane blocks for the thoracoabdominal region in the recent decade. Ultrasonography for musculoskeletal procedures has been of growing interest because of the major advantage of direct visualization and scanning of various soft tissues and real-time spread in the injectate, thereby enhancing precision and efficacy, reducing risk of trauma and avoidance of radiation. For spine and intra-articular structures, ultrasonography is complicated by the bony shadow artefact and often deep location of the structure, making acquisition of ultrasound image challenging. Despite these difficulties, there is growing interest in applying ultrasonography for cervical spine and sacroiliac joint procedures. Summary Pain intervention under ultrasound guidance is particularly valuable in peripheral and musculoskeletal procedures. There is growing interest of its application in cervical spine and sacroiliac joint. More outcome studies are required in the future to make ultrasound-guided pain intervention as the established procedure. Correspondence to Philip Peng, MBBS, FRCPC, Founder (Pain Medicine), Department of Anesthesia and Pain Medicine, University of Toronto, University Health Network-Toronto Western Hospital, McL 2-405, 399 Bathurst Street, Toronto, ON, Canada M5T 2S8. Tel: +1 416 603 5118; fax: +1 416 603 6494; e-mail: Philip.peng@uhn.ca Copyright © 2018 YEAR Wolters Kluwer Health, Inc. All rights reserved.

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Drug selection for ambulatory procedural sedation

Purpose of review Ambulatory procedural sedation is used to relieve anxiety, pain and discomfort in a broad spectrum of patients during many types of diagnostic or therapeutic procedures. This review focuses on recent comparative studies of commonly used and new drugs for adult ambulatory sedation. Recent findings Midazolam and propofol are commonly used for ambulatory sedation. Their pharmacological properties offer many advantages and there is much experience with their use. Ketamine can be a useful addition to hypnotic drugs but the advantage of the use of ketofol (a mixture of propofol and ketamine) is, although often practiced, difficult to assess. Dexmedetomidine is a relatively new sedative drug and many studies suggest advantages. New findings about its effects, however, show that the hemodynamic consequences of the use of dexmedetomidine may last for several hours. New sedative drugs for procedural sedation are still being developed: remimazolam has many properties that would make it an ideal sedative and has been studied in a phase 3 study. Summary The properties that would constitute the ideal sedative have yet to be combined in one drug. The selection of the drugs used for ambulatory sedation depends on many factors such as procedure type, patient characteristics and the expectations of patients and the healthcare provider. Because of this, the literature cannot yet provide a definitive answer to the question which drug is best selected in a specific situation. Correspondence to Clemens R.M. Barends, MD, Department of Anaesthesiology, University of Groningen, University Medical Centre Groningen, P.O. Box 30001, 9700 RB Groningen, The Netherlands. Tel: +31 50 361 6161; e-mail: c.r.m.barends@umcg.nl Copyright © 2018 YEAR Wolters Kluwer Health, Inc. All rights reserved.

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Rebound pain after regional anesthesia in the ambulatory patient

Purpose of review Regional anesthesia is popular in ambulatory setting allowing safe and fast recovery. The problem of 'rebound pain', that is very severe pain when peripheral nerve block (PNB) wears off represents a clinically relevant problem and a cause of increased healthcare resource utilization. This review tries to make the point on a not so rare, unwanted and often neglected side effect of PNB. Recent findings The major finding is the lack of large prospective studies. Incidence of rebound pain is unknown but could reach 40% of patients at PNB resolution. To date, pathophysiological mechanisms remain debated: mechanical and chemical (proinflammatory effect of local anesthetics) nerve insult caused by PNB in predisposed patients (with severe preoperative pain, younger patients). Effective preventive strategies also are missing (e.g. role of analgesic adjuvants in PNB). Long-term consequences in term of functional recovery and persistent pain have not been demonstrated. Interview of patients has underlined the need of information and education about PNB and postoperative analgesia. Summary Patients' report of excruciating pain and major distress when PNB wears off questions the quality of current anesthesia practice in ambulatory setting. Rebound pain unanswered questions are challenging in the area of perioperative medicine. Correspondence to Patricia Lavand'homme, MD, PhD, Department of Anesthesiology, Cliniques Universitaires St Luc – University Catholic of Louvain, Av Hippocrate 10, B-1200, Brussels, Belgium. Tel: +32 2 764 18 21; fax: +32 2 764 36 99; e-mail: patricia.lavandhomme@uclouvain.be Copyright © 2018 YEAR Wolters Kluwer Health, Inc. All rights reserved.

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Neuromonitoring in the ambulatory anesthesia setting: a pro–con discussion

Purpose of review Various neurologically focused monitoring modalities such as processed electroencephalography (pEEG), tissue/brain oxygenation monitors (SbO2), and even somatosensory evoked responses have been suggested as having the potential to improve the well tolerated and effective delivery of care in the setting of outpatient surgery. The present article will discuss the pros and cons of such monitors in this environment. Recent findings There is a paucity of evidence from rigorous, well designed clinical trials demonstrating that the routine use of any neuromonitoring technique in an ambulatory surgery setting leads to meaningful cost savings or a reduction in morbidity or mortality. Summary The use of advanced neuromonitoring techniques (primarily pEEG) may be considered reasonable in two instances: for the prevention of intraoperative awareness during the administration of total intravenous anesthesia coupled with the use of a neuromuscular blocking drug, and for the prevention of relative drug overdose (and possibly postoperative delirium) in the elderly. Correspondence to Peter A. Goldstein, MD, C.V. Starr Laboratory for Molecular Neuropharmacology, Department of Anesthesiology, Weill Cornell Medicine, 1300 York Avenue, Room A-1050, New York, NY 10065, USA. Tel: +1 212 746 5325; fax: +212 746 4879; e-mail: pag204@med.cornell.edu Copyright © 2018 YEAR Wolters Kluwer Health, Inc. All rights reserved.

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