Modulatory effects of neuropeptides on pentylenetetrazol-induced epileptic seizures and neuroinflammation in rats

Kılınç, Erkan; Güneş, Handan

doi:10.1590/1806-9282.65.9.1188

Cited by 16 publications

(8 citation statements)

References 17 publications

(13 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“… 93 A large number of protein factors act on vasculature including fibroblast growth factors, neuropeptides as calcitonin gene-related peptide (CGRP), and substance-P (SP), vascular endothelial growth factors (VEGF), platelet-derived growth factor, and angiopoietins. 94 Proteins of the VEGF family possess potent vascular effects increasing the permeability of the BBB via the NO-synthase pathway 95 and inducing excessive angiogenesis, as evident in patients with temporal lobe epilepsy. 96 Receptors for VEGF have been localized in neurons, vascular endothelium, and glia.…”

Section: Discussionmentioning

confidence: 99%

1,3,4, Oxadiazole Compound A3 Provides Robust Protection Against PTZ-Induced Neuroinflammation and Oxidative Stress by Regulating Nrf2-Pathway

Alvi¹,

Shah²,

Muhammad³

et al. 2021

JIR

View full text Add to dashboard Cite

Background Epilepsy is a common neurological disorder that is characterized by recurrent episodes of seizures. Various studies have demonstrated a direct association between oxidative stress and inflammation in several neurological disorders including epilepsy. This study aimed to investigate the neuroprotective effects of a synthetic 1,3,4, oxadiazole compound A3 against pentylenetetrazole (PTZ)-induced kindling and seizure model. Methodology PTZ was administered in a sub-convulsive dose of 40 mg/kg for 15 days, at 48-hour intervals to male Swiss-Albino mice until animals were fully kindled. Two different doses of A3 (10 mg/kg and 30 mg/kg) were administered to find out the effective dose of A3 and to further demonstrate the relative role of nuclear factor E2-related factor ( Nrf2 ) in the PTZ-induced kindled model. Results Our results demonstrated a compromised antioxidant capacity associated with a low level of catalase (CAT), superoxide dismutase (SOD), glutathione (GST), and glutathione S-transferase (GSH) in the kindled group. However, the PTZ-induced group demonstrated an elevated level of lipid peroxidation (LPO) level parallel to pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNF-α), mediators as cyclooxygenase (COX-2), and nuclear factor kappa B (NFκB). Furthermore, the A3 treatment reversed these changes and overexpressed the antioxidant Nrf2 gene and its downstream HO-1 . To further investigate the involvement of Nrf2 , we employed an Nrf2 -inhibitor, ie, all-trans retinoic acid (ATRA), that further aggravated the PTZ toxicity. Moreover, vascular endothelial growth factor (VEGF) expression was evaluated to assess the extent of BBB disruption. Conclusion The findings of this study suggest that A3 could mediate neuroprotection possibly by activating Nrf2 dependent downregulation of inflammatory cascades.

show abstract

Section: Discussionmentioning

confidence: 99%

1,3,4, Oxadiazole Compound A3 Provides Robust Protection Against PTZ-Induced Neuroinflammation and Oxidative Stress by Regulating Nrf2-Pathway

Alvi¹,

Shah²,

Muhammad³

et al. 2021

JIR

View full text Add to dashboard Cite

show abstract

“…Ghrelin significantly reduced the elevated plasma calcitonin gene-related peptide (CGRP), substance P, interleukin (IL)-6, tumor necrosis factor (TNF)-α, and IL-1β in the PTZ rat model [ 117 , 118 ]. Additionally, ghrelin inhibited KA-induced increases in TNF-α, IL-1β and cyclooxygenase-2 (COX2) mRNA levels in CA1 and CA3 in the i.p.…”

Section: Molecular Mechanisms-of-actionmentioning

confidence: 99%

Targeting the Ghrelin Receptor as a Novel Therapeutic Option for Epilepsy

et al. 2021

View full text Add to dashboard Cite

Epilepsy is a neurological disease affecting more than 50 million individuals worldwide. Notwithstanding the availability of a broad array of antiseizure drugs (ASDs), 30% of patients suffer from pharmacoresistant epilepsy. This highlights the urgent need for novel therapeutic options, preferably with an emphasis on new targets, since “me too” drugs have been shown to be of no avail. One of the appealing novel targets for ASDs is the ghrelin receptor (ghrelin-R). In epilepsy patients, alterations in the plasma levels of its endogenous ligand, ghrelin, have been described, and various ghrelin-R ligands are anticonvulsant in preclinical seizure and epilepsy models. Up until now, the exact mechanism-of-action of ghrelin-R-mediated anticonvulsant effects has remained poorly understood and is further complicated by multiple downstream signaling pathways and the heteromerization properties of the receptor. This review compiles current knowledge, and discusses the potential mechanisms-of-action of the anticonvulsant effects mediated by the ghrelin-R.

show abstract

“…MC activation induces release of peptides from peripheral nerve terminals, including bradykinin, substance P (SP) and vasoactive intestinal peptide (VIP), gene-related peptide (CGRP) and amines, such as histamine and serotonin, which contribute to inflammation-mediated exacerbation of allergic reactions [ 108 , 109 ]. Furthermore, neuropeptides, such as CGRP, SP and VIP, also lead to the release of numerous inflammatory mediators from MCs through degranulation as a result of MC mediator-mediated nerve activation, which in turn enhances neurogenic inflammation and pain perception [ 108 , 110 , 111 ].…”

Section: Interaction Between Mcs and Nerve Endings Ascends Acupunctur...mentioning

confidence: 99%

Activation of Subcutaneous Mast Cells in Acupuncture Points Triggers Analgesia

Wang

et al. 2022

Cells

View full text Add to dashboard Cite

This review summarizes experimental evidence indicating that subcutaneous mast cells are involved in the trigger mechanism of analgesia induced by acupuncture, a traditional oriental therapy, which has gradually become accepted worldwide. The results are essentially based on work from our laboratories. Skin mast cells are present at a high density in acupuncture points where fine needles are inserted and manipulated during acupuncture intervention. Mast cells are sensitive to mechanical stimulation because they express multiple types of mechanosensitive channels, including TRPV1, TRPV2, TRPV4, receptors and chloride channels. Acupuncture manipulation generates force and torque that indirectly activate the mast cells via the collagen network. Subsequently, various mediators, for example, histamine, serotonin, adenosine triphosphate and adenosine, are released from activated mast cells to the interstitial space; they or their downstream products activate the corresponding receptors situated at local nerve terminals of sensory neurons in peripheral ganglia. The analgesic effects are thought to be generated via the reduced electrical activities of the primary sensory neurons. Alternatively, these neurons project such signals to pain-relevant regions in spinal cord and/or higher centers of the brain.

show abstract

Modulatory effects of neuropeptides on pentylenetetrazol-induced epileptic seizures and neuroinflammation in rats

Cited by 16 publications

References 17 publications

1,3,4, Oxadiazole Compound A3 Provides Robust Protection Against PTZ-Induced Neuroinflammation and Oxidative Stress by Regulating Nrf2-Pathway

1,3,4, Oxadiazole Compound A3 Provides Robust Protection Against PTZ-Induced Neuroinflammation and Oxidative Stress by Regulating Nrf2-Pathway

Targeting the Ghrelin Receptor as a Novel Therapeutic Option for Epilepsy

Activation of Subcutaneous Mast Cells in Acupuncture Points Triggers Analgesia

Contact Info

Product

Resources

About