TRESK channel activation ameliorates migraine-like pain via modulation of CGRP release from the trigeminovascular system and meningeal mast cells in experimental migraine models.

Aims: Accumulating evidence indicates the involvement of TRESK potassium channels in migraine, however, effects of TRESK activation on migraine-related mechanisms remain unclear. We explored effects of TRESK channel modulation on migraine-related behavioral and molecular markers in in-vivo and ex-vivo rat models of migraine.

Main Methods: The selective TRESK activator cloxyquin at different doses, the TRESK inhibitor A2764, and the migraine drug sumatriptan were tested alone or in different combinations in nitroglycerin (NTG)-induced in-vivo model, and in ex-vivo meningeal, trigeminal ganglion and brainstem preparations in which CGRP release was induced by capsaicin.

Effects of Probiotic Bacteria on Central Neuronal Activation in Experimental Colitis.

Background: Brain-gut axis dysregulation is observed in inflammatory bowel disease. However, the effect of altered gut flora on neuro- immunomodulation and its role in the pathogenesis of inflammatory bowel disease are unknown. The aims of this study are to determine (i) whether colitis modifies the expression of c-fos, a marker of general neuronal activation in the brain and (ii) whether this activation could be modulated by probiotic bacteria.

The Potential Therapeutic Effects of Agmatine, Methylprednisolone, and Rapamycin on Experimental Spinal Cord Injury.

Objective: In spinal cord injury (SCI), the primary mechanical damage leads to a neuroinflammatory response and the secondary neuronal injury occurs in response to the release of reactive oxygen species (ROS). In addition to the suppression of inflammation, autophagy plays a significant role in the survival of neurons during secondary SCI. The present study aimed to examine the anti-inflammatory and autophagic effects of agmatine and rapamycin in SCI and to compare the results with methylprednisolone (MP) used in the clinic.

Mast cell activation ameliorates pentylenetetrazole-induced seizures in rats: The potential role for serotonin.

Neuroinflammation plays a key role in the pathogenesis of epilepsy, but the underlying mechanisms are not well understood. Mast cells are multifunctional immune cells that are also activated by stress. The effects of activated mast cells on epileptogenesis are not yet known.

Thymoquinone Inhibits Neurogenic Inflammation Underlying Migraine Through Modulation of Calcitonin Gene-Related Peptide Release and Stabilization of Meningeal Mast Cells in Glyceryltrinitrate-Induced Migraine Model in Rats.

Two main contributors of sterile neurogenic inflammation underlying migraine pain, calcitonin gene-related peptide (CGRP), and meningeal mast cells (MMCs) play a key role in the activation of the inflammatory cascade resulting in the sensitization of trigeminal nociceptors. It is well established that phytochemical agent thymoquinone exhibits multiple anti-inflammatory effects in different in vitro and in vivo models of neuroinflammation. But its effects on the CGRP release and meningeal mast cells are unknown.

Shared Fate of Meningeal Mast Cells and Sensory Neurons in Migraine.

Migraine is a primary headache disorder which has complex neurogenic pathophysiological mechanisms still requiring full elucidation. The sensory nerves and meningeal mast cell couplings in the migraine target tissue are very effective interfaces between the central nervous system and the immune system. These couplings fall into three categories: intimacy, cross-talk and a shared fate.

Activation of P2X7 Receptors in Peritoneal and Meningeal Mast Cells Detected by Uptake of Organic Dyes: Possible Purinergic Triggers of Neuroinflammation in Meninges.

Extracellular ATP activates inflammasome and triggers the release of multiple cytokines in various immune cells, a process primarily mediated by P2X7 receptors. However, the expression and functional properties of P2X7 receptors in native mast cells in tissues such as meninges where migraine pain originates from have not been explored. Here we report a novel model of murine cultured meningeal mast cells and using these, as well as easily accessible peritoneal mast cells, studied the mechanisms of ATP-mediated mast cell activation.

4-(3,4-dihydroxybenzoyloxymethyl)phenyl-O-β-D-glucopyranoside effect in liver regeneration.

Following an injury or resection, the mammalian liver has the capacity to regain its former volume and functioning by restoring itself. Studies have demonstrated that antioxidants play a role in hepatic regeneration. This study investigated the effect of 4-(3,4-dihydroxybenzoyloxymethyl) phenyl-O-β-D-glucopyranoside (PG) obtained from Origanum micranthum on liver regeneration.

Salmon calcitonin ameliorates migraine pain through modulation of CGRP release and dural mast cell degranulation in rats.

The exact mechanism of migraine pathophysiology still remains unclear due to the complex nature of migraine pain. Salmon calcitonin (SC) exhibits antinociceptive effects in the treatment of various pain conditions. In this study, we explored the mechanisms underlying the analgesic effect of salmon calcitonin on migrane pain using glyceryltrinitrate (GTN)-induced model of migraine and ex vivo meningeal preparations in rats.

The effect of kisspeptin on spermatogenesis and apoptosis in rats.

Background/aim: To study the effect of kisspeptin, a gonadotropin release stimulator, on the testicular tissue of the rat.

Materials And Methods: Four groups were formed as follows: control, Kiss-10 501397645907nmol administration for 1 day, Kiss-10 administration for 13 days, and one last group kept for 7 days following Kiss-10 applied for 13 days. Testicular tissues were stained with hematoxylin-eosin, periodic acid Schiff, Masson trichrome staining, terminal deoxynucleotidyl transferased UTP nick-end labeling, and Ki-67 immune staining.

Vasoactive Intestinal peptide modulates c-Fos activity in the trigeminal nucleus and dura mater mast cells in sympathectomized rats.

Neurogenic inflammation in the dura mater caused by trigeminal nociceptive activation has been implicated in the pathophysiology of migraine. Vasoactive intestinal polypeptide (VIP) is a powerful neuroprotective neuropeptide that can modulate mast cell behavior. Migraine is also associated with sympathetic insufficiency.

The preventive effect of low molecular weight heparin on CCL₄-induced necrosis and apoptosis in rat liver.

Introduction: Heparin having anti-inflammatory and anti-fibrotic properties may have therapeutic effect on liver injury. The present study investigated the effect of low molecular weight heparin (Enoxaparin) on carbon tetrachloride (CCl₄) induced hepatic necrosis and apoptosis in rats.

Material And Methods: Thirty male rats were divided into 5 groups.

The effects of vasoactive intestinal peptide on dura mater nitric oxide levels and vessel-contraction responses in sympathectomized rats.

Nitric oxide (NO) and neurogenic inflammation in dura mater due to nociceptor activation has been implicated for pathophysiology of primary headache disorders. Development of migraine has also been observed in patients treated with ganglion blockage for sympathetic reflex dystrophy. Vasoactive intestinal peptide (VIP) is an antioxidant, anti-inflammatory, and neuroprotective neuropeptide.

Mast cells: target and source of neuropeptides.

Mast cells, originating from bone marrow pluripotential cells are generally populated near to strategic locations of mammalian body. They store a wide variety of biologically active molecules in their granules and also can de novo synthesize an additional spectrum of mediators, depending on their microenvironment, phenotype and status. Mast cells have numerous receptors that can trigger a wide spectrum of cellular responses, some of them which can be preprogrammed against specific pathogens.

Sympathetic skin responses of the face and neck evoked by electrical stimulation.

The sympathetic skin responses (SSRs) were recorded from different facial regions and neck in 25 subjects evoked by electrical stimulation of the median nerve at the wrist. Recordings from all regions were cross-compared with each other and within right and left sides individually. In one subject postauricular SSR, and in another subject upper lip SSR could not be elicited on both sides.

Passage of VIP/PACAP/secretin family across the blood-brain barrier: therapeutic effects.

In recent years, VIP/PACAP/secretin family has special interest. Family members are vasoactive intestinal peptide (VIP), pituitary adenylate cyclase-activating polypeptide (PACAP), secretin, glucagon, glucagon like peptide-1 (GLP(1)), GLP(2), gastric inhibitory peptide (GIP), growth hormone releasing hormone (GHRH or GRF), and peptide histidine methionine (PHM). Most of the family members present both in central nervous system (CNS) and in various peripheral tissues.

Protective effect of vasoactive intestinal peptide on testicular torsion-detorsion injury: association with heparin-containing mast cells.

Objectives: To elucidate the action of vasoactive intestinal peptide (VIP) on detorsion injury and the heterogeneity of mast cells in the testes of rats.

Methods: Prepubertal male Sprague-Dawley rats were used in six groups. Group 1 was the control group (sham operation); group 2 had 2 hours of torsion; group 3, 2 hours of torsion and 1 hour of detorsion after administration of saline; group 4 had 2 hours of torsion and 4 hours of detorsion after administration of saline; group 5, 2 hours of torsion and 1 hour of detorsion after administration of intraperitoneal VIP (25 ng/kg); and group 6, 2 hours of torsion and 4 hours of detorsion after intraperitoneal VIP.

Effects of sepsis on mast cells in rat dura mater: influence of L-NAME and VIP.

1. The influence of lipopolysaccharide (LPS)-induced sepsis on the various mast cell phenotypes of rat dura mater were examined both by immunohistochemical and biochemical methods. 2.

Vasoactive intestinal peptide inhibits degranulation and changes granular content of mast cells: a potential therapeutic strategy in controlling septic shock.

Vasoactive intestinal peptide (VIP) has potent protective activity against sepsis and increases the survival rate of septic rats and mice. The present study was planned to evaluate the effect of VIP on mast cell activity, histamine and methylhistamine levels and oxidative stress in the liver and kidneys of septic rats. The effect of VIP was compared to that of nitric oxide synthesis inhibition, previously tested extensively in septic shock models, with doubtful benefit.