Effect of probenecid on the pain-related behaviour and morphological markers in orofacial formalin test of the rat.

Unlabelled: Probenecid has been widely used in the treatment of gout, but evidence suggests that it may also have antinociceptive effects in different inflammatory and pain conditions. We examined the potential modulatory effects of probenecid on behavioural and morphological markers in the orofacial formalin test of the rat. One hour after pre-treatment with vehicle or probenecid (1 mmol/kg body weight) intraperitoneally, 50μl 1.

Pre-treatment with new kynurenic acid amide dose-dependently prevents the nitroglycerine-induced neuronal activation and sensitization in cervical part of trigemino-cervical complex.

The systemic administration of nitroglycerine induces attacks in migraineurs and is able to activate and sensitize the trigeminal system in animals involving glutamate and α7-nicotinic acetylcholine receptors, among others. Kynurenic acid is one of the endogenous glutamate receptor antagonists, and exerts inhibitory action on the α7-nicotinic acetylcholine receptors. Since kynurenic acid penetrates the blood-brain barrier poorly, therefore a newly synthesized kynurenic acid amide, N-(2-N-pyrrolidinylethyl)-4-oxo-1H-quinoline-2-carboxamide hydrochloride (KYNAa) was used with such a side-chain substitution to facilitate brain penetration in our study.

Digital PCR to determine the number of transcripts from single neurons after patch-clamp recording.

Whole-cell patch-clamp recording enables detection of electrophysiological signals from single neurons as well as harvesting of perisomatic RNA through the patch pipette for subsequent gene expression analysis. Amplification and profiling of RNA with traditional quantitative real-time PCR (qRT-PCR) do not provide exact quantitation due to experimental variation caused by the limited amount of nucleic acid in a single cell. Here we describe a protocol for quantifying mRNA or miRNA expression in individual neurons after patch-clamp recording using high-density nanocapillary digital PCR (dPCR).

Effect of systemic kynurenine on cortical spreading depression and its modulation by sex hormones in rat.

Background: The aura symptoms in migraine are most likely due to cortical spreading depression (CSD). CSD is favored by NMDA receptor activation and increased cortical excitability. The latter probably explains why migraine with aura may appear when estrogen levels are high, like during pregnancy.

Neuroprotective effects of L-carnitine in a transgenic animal model of Huntington's disease.

Huntington's disease (HD) is an autosomal dominant inherited disorder, caused by an expanded polyglutamine region of a protein called huntingtin. The excitotoxicity, oxidative damage, mitochondrial dysfunction and altered membrane transport may have important roles in the pathogenesis of HD. L-carnitine plays a role in facilitating the mitochondrial transport of fatty acids, but it also protects the cells from oxidative damage.

Kynurenate derivative attenuates the nitroglycerin-induced CamKIIα and CGRP expression changes.

Objective: To examine the efficacy of L-kynurenine and a novel kynurenic acid derivative on the nitroglycerin-induced calmodulin-dependent protein kinase II alpha (CamKIIalpha) and calcitonin gene-related peptide (CGRP) expression changes in the rat caudal trigeminal nucleus.

Background: Systemic administration of the nitric oxide donor nitroglycerin can trigger an attack in migraineurs. In the rat, nitroglycerin activates second-order neurons in the caudal trigeminal nucleus, and increases expression of the CamKIIalpha and decreases that of the CGRP there.

Modulatory effects of probenecid on the nitroglycerin-induced changes in the rat caudal trigeminal nucleus.

Four hours after systemic administration of the nitric oxide donor nitroglycerin (10 mg/kg bodyweight, s.c.), the neurons of the rat caudal trigeminal nucleus are activated, the area covered by calcitonin gene-related peptide (CGRP)-immunoreactive fibres is decreased and the neuronal nitric oxide synthase (nNOS)- and the calmodulin-dependent protein kinase II alpha (CamKIIalpha)-immunopositive neurons in the same area are increased.

Valproate ameliorates the survival and the motor performance in a transgenic mouse model of Huntington's disease.

Huntington's disease (HD) is one of the chronic devastating neurodegenerative disorders. The pathophysiological processes clearly involve both excitotoxicity and reduced gene transcription due to the decreased level of histone acetylation, accompanied by the loss of gamma-aminobutyric acidergic (GABAergic) medium-sized spiny neurons in the striatum as a pathological hallmark of HD. Thus, the antiepileptic drug valproate, which has proved GABAergic, antiexcitotoxic and histone deacetylase inhibitor effects, might be of value by exerting a beneficial neuroprotective effect.

l-kynurenine combined with probenecid and the novel synthetic kynurenic acid derivative attenuate nitroglycerin-induced nNOS in the rat caudal trigeminal nucleus.

Systemic administration of the nitric oxide (NO) donor nitroglycerin (NTG) triggers a delayed attack without aura in many migraineurs, but not in healthy volunteers. In rats, 4 h after the systemic administration of NTG (10 mg/kg bw, s.c.

Neuroprotective effects of probenecid in a transgenic animal model of Huntington's disease.

Huntington's disease (HD) is an autosomal dominantly inherited disorder, caused by an expanded polyglutamine region of a protein called huntingtin. The excitotoxicity, oxidative damage and altered membrane transport may have an important role in the pathogenesis of HD. Probenecid is a non-selective inhibitor of multidrug resistance-associated proteins, but it also inhibits organic anion transporters.

The role of kynurenines in disorders of the central nervous system: possibilities for neuroprotection.

The metabolism of tryptophan mostly proceeds through the kynurenine pathway. The biochemical reaction includes both an agonist (quinolinic acid) at the N-methyl-d-aspartate receptor and an antagonist (kynurenic acid). Besides the N-methyl-d-aspartate antagonism, an important feature of kynurenic acid is the blockade of the alpha7-nicotinic acetylcholine receptor and its influence on the alpha-amino-3-hydroxy-5-methylisoxazole-4-proprionic acid receptor.

Selective inhibition of cyclooxygenase-2 attenuates nitroglycerin-induced calmodulin-dependent protein kinase II alpha in rat trigeminal nucleus caudalis.

The nitric oxide donor, nitroglycerin (NTG) can trigger a migraine attack, after a delay of several hours in migraineurs, but not in healthy people. This long delay does not favor a pure vasodilatatory action. In rats, subcutaneous administration of NTG (10mg/kg) significantly and selectively increases the number of calmodulin-dependent protein kinase II alpha (CamKIIalpha)-immunoreactive neurons in the trigeminal caudal nucleus (TNC) after 4h.

Effects of valproate on the dopaminergic system in mice.

Valproate is a widely used antiepileptic drug with a known tremor-inducing effect. In this study, we tested the behavioral changes induced by valproate and its effect on the dopaminergic cells in the substantia nigra of mice. This treatment led to a spontaneous locomotor activity, while the explorative behavior was unaltered.

Cox-2 inhibitor attenuates NO-induced nNOS in rat caudal trigeminal nucleus.

Objective: The aim of the present study was to determine which isoform of the cyclooxygenase (COX) enzyme plays a role in the neuronal nitric oxide synthase (nNOS) activation caused by nitroglycerin (NTG), in the most caudal part of the trigeminal caudal nucleus (TNC) of the rat.

Background: Nitric oxide donor, NTG, can trigger migraine attack in migraineurs, but not in healthy persons. In rats, subcutaneous administration of NTG (10 mg/kg) increases significantly the number of nNOS-immunoreactive neurons in the TNC after 4 hours, which could be attenuated by acetyl-salicylate (Aspirin), a nonselective COX-inhibitor.