Visualization and Characterization of the Brain Regional Heterogeneity of Astrocyte-Astrocyte Structural Interactions by Using Improved Iontophoresis with Dual-Fluorescent Dyes.

Astrocytes are morphologically intricate cells and actively modulate the function of the brain. Through numerous fine processes, astrocytes come into contact with neurons, blood vessels, and other glia cells. Emerging evidence has shown that astrocytes exhibit brain regional diversity in their morphology, transcriptome, calcium signaling, and functions.

Prolonged exposure of neonatal mice to sevoflurane leads to hyper-ramification in microglia, reduced contacts between microglia and synapses, and defects in adult behavior.

Background: Prolonged exposure to general anesthetics during development is known to cause neurobehavioral abnormalities, but the cellular and molecular mechanisms involved are unclear. Microglia are the resident immune cells in the central nervous system and play essential roles in normal brain development.

Materials And Methods: In the study, postnatal day 7 (P7) C57BL/6 mice were randomly assigned to two groups.

QX-OH/Levobupivacaine: A Structurally Novel, Potent Local Anesthetic Produces Fast-Onset and Long-Lasting Regional Anesthesia in Rats.

Purpose: Local anesthetics (LAs) are an important alternative for postoperative analgesia; however, the short duration of LAs limits their use. Thus, we previously developed LL-1, a mixture of QX-OH and levobupivacaine (LB) that produces regional anesthesia for more than 10 h in rats. The aim of this study is to investigate the long-acting mechanism of LL-1 in vivo and in vitro.

Inhibiting Hv1 channel in peripheral sensory neurons attenuates chronic inflammatory pain and opioid side effects.

Both opioids and nonsteroidal anti-inflammatory drugs (NSAIDS) produce deleterious side effects and fail to provide sustained relief in patients with chronic inflammatory pain. Peripheral neuroinflammation (PN) is critical for initiation and development of inflammatory pain. A better understanding of molecular mechanisms underlying PN would facilitate the discovery of new analgesic targets and the development of new therapeutics.

Sodium leak channel contributes to neuronal sensitization in neuropathic pain.

Neuropathic pain affects up to 10 % of the total population and no specific target is ideal for therapeutic need. The sodium leak channel (NALCN), a non-selective cation channel, mediates the background Na leak conductance and controls neuronal excitability and rhythmic behaviors. Here, we show that increases of NALCN expression and function in dorsal root ganglion (DRG) and dorsal spinal cord contribute to chronic constriction injury (CCI)-induced neuropathic pain in rodents.

Deficiency of Mitochondrial Functions and Peroxidation of Frontoparietal Cortex Enhance Isoflurane Sensitivity in Aging Mice.

: Hypersensitivity to general anesthetics may predict poor postoperative outcomes, especially among the older subjects. Therefore, it is essential to elucidate the mechanism underlying hypersensitivity to volatile anesthetics in the aging population. Given the fact that isoflurane sensitivity increases with aging, we hypothesized that deficiencies of mitochondrial function and elevated oxidative levels in the frontoparietal cortex may contribute to the enhanced sensitivity to isoflurane in aging mice.

TREK Channel Family Activator with a Well-Defined Structure-Activation Relationship for Pain and Neurogenic Inflammation.

TWIK-related K (TREK) channels are potential analgesic targets. However, selective activators for TREK with both defined action mechanism and analgesic ability for chronic pain have been lacking. Here, we report (1,3)-3-((4-(6-methylbenzo[]thiazol-2-yl)phenyl)carbamoyl)cyclopentane-1-carboxylic acid (C3001a), a selective activator for TREK, against other two-pore domain K (K2P) channels.

Activation of the RAS/B-RAF-MEK-ERK pathway in satellite glial cells contributes to substance p-mediated orofacial pain.

The cross talk between trigeminal ganglion (TG) neurons and satellite glial cells (SGCs) is crucial for the regulation of inflammatory orofacial pain. Substance P (SP) plays an important role by activating neurokinin (NK)-I receptors in this cross talk. The activation of extracellular signal-regulated kinase (ERK) 1/2, protein kinase A (PKA) and protein kinase C (PKC) in neurons and SGCs of peripheral ganglions by peripheral inflammation is associated with inflammatory hypersensitivity.

The P2Y receptor in the trigeminal ganglion contributes to the maintenance of inflammatory pain.

P2Y purinergic receptors expressed in neurons and satellite glial cells (SGCs) of the trigeminal ganglion (TG) contribute to inflammatory and neuropathic pain. P2Y receptor expression is reported in the spinal cord, dorsal root ganglion (DRG), and TG. In present study, the role of P2Y receptor in the TG in inflammatory orofacial pain of Sprague-Dawley (SD) rats was investigated.

Activation of mitogen-activated protein kinases in satellite glial cells of the trigeminal ganglion contributes to substance P-mediated inflammatory pain.

Inflammatory orofacial pain, in which substance P (SP) plays an important role, is closely related to the cross-talk between trigeminal ganglion (TG) neurons and satellite glial cells (SGCs). SGC activation is emerging as the key mechanism underlying inflammatory pain through different signalling mechanisms, including glial fibrillary acidic protein (GFAP) activation, phosphorylation of mitogen-activated protein kinase (MAPK) signalling pathways, and cytokine upregulation. However, in the TG, the mechanism underlying SP-mediated orofacial pain generated by SGCs is largely unknown.

Astroglial dysfunctions drive aberrant synaptogenesis and social behavioral deficits in mice with neonatal exposure to lengthy general anesthesia.

Lengthy use of general anesthetics (GAs) causes neurobehavioral deficits in the developing brain, which has raised significant clinical concerns such that the United States Food and Drug Administration (FDA) is warning on the use of GAs in children younger than 3 years. However, the molecular and cellular mechanisms for GAs-induced neurotoxicity remain largely unknown. Here, we report that sevoflurane (Sevo), a commonly used GA in pediatrics, caused compromised astrocyte morphogenesis spatiotemporally correlated to synaptic overgrowth, with reduced synaptic function in developing cortex in a regional-, exposure-length-, and age-specific manner.

Capsazepine prolongation of the duration of lidocaine block of sensory transmission in mice may be mediated by modulation of HCN channel currents.

Background And Objectives: Hyperpolarization-activation cyclic nucleotide-gated (HCN) channels contribute to the effects of lidocaine. Capsazepine (CPZ), a competitive inhibitor of capsaicin of transient receptor potential vanilloid-1 channel, has also been found to inhibit HCN channel currents ( ). This study was designed to investigate whether CPZ could prolong durations of lidocaine in regional anesthesia.

[Xylazine Produced Analgesic Effect via Inhibits Hyperpolarization-activated Cyclic Nucleotide-gated Ion Channels Currents].

Objective: To investigate the analgesic mechanism of xylazine by inhibiting the activation of hyperpolarized cyclic nucleotide-gated (HCN) ion channels.

Methods: HCN subchannel 1 (HCN1) knockout mice (HCN1) and HCN1 wild type mice (HCN1) were intraperitoneally injected with physiological saline and xylazine (10, 20, 30, and 40 mg/kg). Mechanical pain test and tail flick test were used to test the analgesic effect of xylazine by using the percentage of the maximal possible effect (%MPE); The control group and test groups of different concentrations of xylazine (12.

P2Y receptor is functionally expressed in satellite glial cells and mediates interleukin-1β and chemokine CCL2 secretion.

Satellite glial cells (SGCs) activation in the trigeminal ganglia (TG) is critical in various abnormal orofacial sensation in nerve injury and inflammatory conditions. SGCs express several subtypes of P2 purinergic receptors contributing to the initiation and maintenance of neuropathic pain. The P2Y receptor, a G-protein-coupled receptor activated by uridine diphosphate (UDP)-glucose and other UDP sugars, mediates various physiologic events such as immune, inflammation, and pain.

Effect of Titanium Particles on the Voltage-Gated Potassium Channel Currents in Trigeminal Root Ganglion Neurons.

Purpose: Titanium (Ti) is the key material used in dental implants because of its excellent biocompatibility. But wear and corrosion Ti particles had been widely reported to induce inflammation and promote bone absorption. However, little information is known about the damage of Ti particles on neurons.

Neglected Hydrophobicity of Dimethanediyl Group in Peptide Self-Assembly: A Hint from Amyloid-like Peptide GNNQQNY and Its Derivatives.

Besides typical hydrophobic amino acids providing hydrophobic interactions, glutamine as a hydrophilic amino acid has also been known to be an important element in many self-assembling peptides, but it is still not clear how this particular amino acid contributes to the self-assembling process. We supposed that the dimethanediyl group in the side chain of glutamine could provide hydrophobic interaction for peptide self-assembly. To prove this hypothesis, we used the GNNQQNY peptide and its derivatives as examples to show the importance of the dimethanediyl group for peptide self-assembly.

Characterization of Specific Roles of Sodium Channel Subtypes in Regional Anesthesia.

Background And Objectives: Commonly used local anesthetics (eg, lidocaine) are nonselective in blocking sodium channel subtypes, potentially resulting in adverse events, such as prolonged muscle paralysis and unstable hemodynamics. Subtype-selective sodium channel block might avoid these unwanted adverse effects while preserving desirable anesthetic effects. The contributions of sodium channel subtypes in different components of regional anesthesia are unclear and this study assumed that selective sodium channel subtype block might produce selective nerve block.

Emulsified halothane produces long-term epidural anesthetic effect: a study in rabbits.

Previous studies have demonstrated that volatile anesthetics could produce local anesthesia. Emulsified isoflurane at 8% has been reported to produce epidural anesthetic effect in rabbits. This study was designed to investigate the long-term epidural anesthetic effect of emulsified halothane in rabbits.

The effect of gliquidone on KATP channels in pancreatic β-cells, cardiomyocytes, and vascular smooth muscle cells.

Aims: Sulfonylurea drugs exert an insulinotropic effect through ATP-sensitive potassium (KATP) channel inhibition in pancreatic islet cells. These channels are also expressed in cardiomyocytes and vascular smooth muscle cells (VSMCs), suggesting potential for adverse cardiovascular effects. We evaluated the effects of Gliquidone (Glq) on sulfonylurea receptors in HIT-T15 cells (SUR1), cardiomyocytes (SUR2A), and VSMCs (SUR2B).

Hyperpolarization-activated cyclic nucleotide-gated channels may contribute to regional anesthetic effects of lidocaine.

Background: Local anesthetics (e.g., lidocaine) have been found to inhibit hyperpolarization-activated cyclic nucleotide-gated (HCN) channels besides sodium channels.

The quaternary lidocaine derivative QX-314 produces long-lasting intravenous regional anesthesia in rats.

Background: The lidocaine derivative, QX-314, produces long-lasting regional anesthesia in various animal models. We designed this study to examine whether QX-314 could produce long-lasting intravenous regional anesthesia (IVRA) in a rat model.

Methods: IVRA was performed on tail of rats.

Emulsified isoflurane enhances thermal transient receptor potential vanilloid-1 channel activation-mediated sensory/nociceptive blockade by QX-314.

Background: QX-314 produces nociceptive blockade, facilitated by permeation through transient receptor potential vanilloid-1 (TRPV1) channels. TRPV1 channel can be activated by noxious heat and sensitized by volatile anesthetics. The authors hypothesized that emulsified isoflurane (EI) could enhance thermal TRPV1 channel activation-mediated sensory/nociceptive blockade by QX-314.

Alterations of voltage-dependent calcium channel currents in basilar artery smooth muscle cells at early stage of subarachnoid hemorrhage in a rabbit model.

Objective: To investigate the changes in the currents of voltage-dependent calcium channels (VDCCs) in smooth muscle cells of basilar artery in a rabbit model of subarachnoid hemorrhage (SAH).

Methods: New Zealand white rabbits were randomly divided into five groups: sham (C), normal (N), 24 hours (S1), 48 hours (S2) and 72 hours (S3) after SAH. Non-heparinized autologous arterial blood (1 ml/kg) was injected into the cisterna magna to create SAH after intravenous anesthesia, and 1 ml/kg of saline was injected into cisterna magna in the sham group.

The common anesthetic, sevoflurane, induces apoptosis in A549 lung alveolar epithelial cells.

Lung alveolar epithelial cells are the first barrier exposed to volatile anesthetics, such as sevoflurane, prior to reaching the targeted neuronal cells. Previously, the effects of volatile anesthetics on lung surfactant were studied primarily with physicochemical models and there has been little experimental data from cell cultures. Therefore it was investigated whether sevoflurane induces apoptosis of A549 lung epithelial cells.

OECs transplantation results in neuropathic pain associated with BDNF regulating ERK activity in rats following cord hemisection.

Background: The olfactory ensheathing cells (OECs) derived from olfactory bulb (OB) may improve motor function after transplantation in injured spinal cord. However, the effects of OEC transplantation on sensory function have not been reported yet. The purpose of this study is to investigate whether OEC transplantation could affect the sensory function and to analyze the underlying mechanism.