Kynurenic acid (KynA), an endogenous antagonist of N‐methyl‐d‐aspartate (NMDA) glutamate receptors, protects the central nervous system in excitotoxic neurological diseases. We hypothesized that the ...inhibition of enteric glutamate receptors by KynA may influence dysmotility in the gastrointestinal tract. Group 1 of healthy dogs served as the sham‐operated control, in group 2, the animals were treated with KynA, while in groups 3 and 4 mechanical colon obstruction was maintained for 7 h. Group 4 was treated with KynA at the onset of ileus. Hemodynamics and motility changes were monitored, and the activities of xanthine oxidoreductase (XOR) and myeloperoxidase (MPO) were determined from tissue samples. Colon obstruction induced a hyperdynamic circulatory reaction, significantly elevated the motility index and increased the mucosal leucocyte accumulation and the XOR activity. The KynA treatment augmented the tone of the colon, permanently decreased the motility index of the giant colonic contractions and reduced the increases in XOR and MPO activities. These effects were concomitant with the in vitroinhibition of XOR activity. In conclusion, KynA antagonizes the obstruction‐induced motility responses and XOR activation in the colon. Inhibition of enteric NMDA receptors may provide an option to influence intestinal hypermotility and inflammatory changes.
Migraine is a common, paroxysmal, highly disabling primary headache disorder. The origin of migraine attacks is enigmatic. Numerous clinical and experimental results suggest that the activation of ...distinct brainstem nuclei is crucial in its pathogenesis, but the primary cause of this activation is not fully understood. We conclude that the initialization of a migraine attack can be explained as an altered function of the neuronal elements of the brainstem nuclei. In light of our findings and the literature data, we can assume that migraine is a subcortical disorder of a specific brainstem area.
A high proportion of research relating to cerebral ischemia focuses on neuroprotection. The application of compounds normally present in the organism is popular, because they do not greatly influence ...the synaptic activity by receptor modulation, and can be administered without serious side effects. Oxaloacetate (OxAc) and acetyl-L-carnitine (ALC) are such favorable endogenous molecules. ALC can exert a protective effect by improving the energy state of the neurons under ischemic conditions. A promising neuroprotective strategy is glutamate scavenging, which can be achieved by the intravenous administration of OxAc. This study involved the possible protective effects of ALC and OxAc in different post-treatment protocols against long-term potentiation (LTP) impairment. Ischemia was induced in rats by 2-vessel occlusion, which led to a decreased LTP relative to the control group. High-dose (200 mg/kg) ALC or OxAc post-treatment resulted in a higher potentiation relative to the 2VO group, but it did not reach the control level, whereas low-dose ALC (100 mg/kg) in combination with OxAc completely restored the LTP function. Many previous studies have concluded that ALC can be protective only as pretreatment. The strategy described here reveals that ALC can also be neuroprotective when utilized as post-treatment against ischemia.
Huntington's disease is an autosomal dominantly inherited progressive neurodegenerative disorder. The mutant gene has been localised to chromosome 4p16.3. The gene product huntingtin is widely ...distributed in both neurones and extraneuronal tissues. The mutation in Huntington's disease involves the expansion of a trinucleotide (CAG) repeat encoding glutamine. The etiology of Huntington's disease is yet unknown but increasing evidence suggests important role of altered gene transcription, mitochondrial dysfunction and excitotoxicity. The expanded polyglutamine stretch leads to a conformational change and abnormal protein-protein interactions. Mutant huntingtin can bind to transcription factors, resulting in reduced levels of acetylated histones. One consequence of this appears to be a decreased expression of genes which may play critical roles in neuronal survival. To date, a number of palliative therapies have been demonstrated to be effective in reducing the motor features, and particularly the chorea, but no treatment is at hand for the other symptoms of Huntington's disease. However, these treatments produce very limited symptomatic benefit. In the absence of disease-modifying treatment, the other avenue is the neural transplantation.However, recent advances in understanding have furnished new hope that a therapeutic strategy may one day be possible.
Background Subdominant hemispheric lesion results neglect syndrome, where the processing of the visual information coming from the contralateral side is damaged. A similar phenomenon is known in ...healthy subjects, called pseudo-neglect. In line bisection task there is a tendency to pay more attention to the left side of space. Method We involved 29 healthy subjects. Landmark task was used in a forced choice paradigm to determine the preferred space side. Then cathodal transcranial direct–current stimulation was used in the right region of posterior–parietal cortex. Landmark task was repeated. Fierro score was used to describe the precise choices and the reaction time was calculated. Results 67% of the subjects showed left pseudo-neglect, 22% showed right pseudo-neglect and in 11% pseudo-neglect was not detected. After the stimulation the number of the incorrect choices was increased ( p < 0.0362) and the reaction time increased in the case of the middle-sectioned line ( p < 0.0126) and in the case of the right-sectioned line ( p < 0.0099). Conclusion Parietal lobe has a crucial role in spatial attention. It can be measured by neurocognitive tests that might serve as a test for the early detection of cognitive impairment. Key message Cathodal stimulation of the parietal lobe can induce a neglect-like symptom.
Introduction To clarify pathophysiology of schizophrenia it is required to decrease the phenomenological heterogeneity, and one of the possible ways is determining neurobiologically valid subgroups. ...Objectives Employing two concurrent methods – Deficit and Nondeficit (Carpenter et al., 1988) vs. cluster S and Z (Szendi et al., 2010) – the group of patients was divided into two subgroups, and brain volumetric peculiarities of the whole mixed group of patients and of these subgroups were compared with the healthy controls and each other. Aims This study aims to possibly reveal the most brain structural anomalies by applying concurrent subgrouping methods of patients, and moreover to confront their validity by the results. Methods High resolution T1 weighted images were performed on n=21 patients with schizophrenia, living integrated in the society and treated in outpatient care, and n=13 healthy control persons. Localised grey matter volumetric deficits were defined with optimised voxel-based morphometry. Results Most areas were revealed in the case of the cluster S, which was characterised by an expansive, bilateral brain structural impairment, which mainly affected the heteromodal and partly the unimodal association cortices. Conclusions This suggests that the expansive impairment of the association cortices could have a determining role in the etiopathogenesis of the unfavourable cluster of patients with schizophrenia. In the literature, an extent of damage commensurable to our observations specifically on association areas has never been detected – and our systematic neurocognitive subgrouping method provided the possibility for this. Financial support for the research was provided by KTIA_NAP_13-2-2014-0020 to Mihály Racsmány.
The main purpose of this study was to facilitate the delivery of kynurenic acid (KYNA) across the blood–brain barrier (BBB) by applying micelles as nanoscale containers. Non-ionic amphiphilic ...molecules were used for preparation of spherical micelles for delivery of kynurenic acid in aqueous solution in physiological condition. It was established that Triton X 100 and Lutensol AP 20 non-ionic surfactants are able to produce stable nanocontainers for delivery of kynurenic acid molecules. The incorporation of KYNA molecules was investigated by dynamic light scattering and the size of micelles were calculated between 5 and 10 nm in 150 mM NaCl and pH 7.5–7.6 solutions. Encapsulated kynurenic acid showed a significantly higher blood–brain barrier permeability compared with non-encapsulated kynurenic acid. The in vivo experiments showed that the encapsulated kynurenic acid is able to display effects within the central nervous system, even after its peripheral administration.
Abstract Background The ‘Multiple Sclerosis Quality of Life Instrument’ (MSQOL-54) was recently validated in Hungarian, on more than 400 multiple sclerosis (MS) patients. The aim of the present study ...was to examine the impact on their overall quality of life (QoL) of the demographic and clinical data on these patients, and their scores on different QoL scales. Methods The Hungarian version of MSQOL-54 was given to patients at the outpatient units at the Department of Neurology, University of Szeged, and two other Hungarian MS centres. Additional data, including the EDSS scores of the patients, and relevant clinical and demographic data, were also collected. Results The questionnaire scales relating to social function, general health, mental health and satisfaction with the sexual function mostly determined the overall QoL ratings. 62.1% of the patients indicated at least one comorbid condition. Depressed patients had a significantly worse quality of life ( p < 0.0001). Conclusions MSQOL-54 is a useful tool for the recognition of possibly treatable factors influencing the QoL, but not assessed by the EDSS. Quality of life data have emerged on more than 400 patients, i.e. a considerable proportion of the Hungarian MS patient population.
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