Anti-absence activity of mGlu1 and mGlu5 receptor enhancers and their interaction with a GABA reuptake inhibitor: effect of local infusions in the somatosensory cortex and thalamus

OBJECTIVE Glutamate and γ-aminobutyric acid (GABA) are the key neurotransmitter systems in the cortical-thalamocortical network, involved in normal and pathologic oscillations such as spike-wave discharges (SWDs), which characterize different forms of absence epilepsy. Metabotropic glutamate (mGlu) and GABA receptors are widely expressed within this network. Herein, we examined the effects of two selective positive allosteric modulators (PAMs) of mGlu1 and mGlu5 receptors, the GABA reuptake inhibitor, tiagabine, and their interaction in the somatosensory cortex and thalamus on SWDs in WAG/Rij rats. METHODS Male WAG/Rij rats were equipped with bilateral cannulas in the somatosensory cortex (S1po) or the ventrobasal (VB) thalamic nuclei, and with cortical electroencephalography (EEG) electrodes. Rats received a single dose of the mGlu1 receptor PAM, RO0711401, or the mGlu5 receptor PAM, VU0360172, various doses of tiagabine, or VU0360172 combined with tiagabine. RESULTS Both PAMs suppressed SWDs regardless of the site of injection. Tiagabine enhanced SWDs when injected into the thalamus, but, unexpectedly, suppressed SWDs in a dose-dependent manner when injected into the cortex. Intracortical co-injection of VU0360172 and tiagabine produced slightly larger effects as compared to either VU0360172 or tiagabine alone. Intrathalamic co-injections of VU0360172 and subthreshold doses of tiagabine caused an antiabsence effect similar to that exhibited by VU0360172 alone in the first 10 min. At 30 min, however, the antiabsence effect of VU0360172 was prevented by subthreshold doses of tiagabine, and the combination produced a paradoxical proabsence effect at 40 and 50 min. SIGNIFICANCE These data (1) show that mGlu1 and mGlu5 receptor PAMs reduce absence seizures acting at both thalamic and cortical levels; (2) demonstrate for the first time that tiagabine, despite its established absence-enhancing effect, reduces SWDs when injected into the somatosensory cortex; and (3) indicate that the efficacy of VU0360172 in the thalamus may be critically affected by the availability of (extra)synaptic GABA

Education of employees in a selected company

This bachelor's work deals with the education of employees in a selected organization like one of the most important tasks in the field of human resources management. Effectiveness and success of the educational process is highly important for each organization. The aim of this bachelor's thesis is to analyse and describe the educational process in the selected organization. My bachelor's thesis includes two parts: a theoretical part and a practical one. The theoretical part will focus on the education and its basic forms and methods. Also in the theoretical part the process of education will be described in details. In the practical part is going to be the presentation of the selected organization and the analysis of the educational process there. Based on the obtained results, at the end of the practical part will be discussed the evaluation and recommendations about possible improvements of the whole education system in the organization

Education of employees in a selected company

Tato bakalářská práce se zabývá vzděláváním zaměstnanců ve vybrané organizaci, jako jedním z nejdůleţitějších úkolů v oblasti řízení lidských zdrojů. Pro kaţdou organizaci také důleţité, aby vzdělávání proběhlo prospěšně a efektivně. Cílem teto bakalářské práce je analyzování a popsání vzdělávacích procesů ve vybrané organizaci. Bakalářská práce obsahuje dvě části: část teoretickou a část praktickou. Teoretická část bude zaměřena na vzdělávání a jeho základní formy a metody. V teoretické části bude detailně popsán proces vzdělávání a jeho jednotlivé fáze. V části praktické bude představení organizace a analyzování procesu vzdělávání v ní probíhajícího. Na základě získaných výsledků budou v závěru popsány hodnocení, návrhy a doporučení ke zlepšení vzdělávacího systému v organizaci.This bachelor's work deals with the education of employees in a selected organization like one of the most important tasks in the field of human resources management. Effectiveness and success of the educational process is highly important for each organization. The aim of this bachelor's thesis is to analyse and describe the educational process in the selected organization. My bachelor's thesis includes two parts: a theoretical part and a practical one. The theoretical part will focus on the education and its basic forms and methods. Also in the theoretical part the process of education will be described in details. In the practical part is going to be the presentation of the selected organization and the analysis of the educational process there. Based on the obtained results, at the end of the practical part will be discussed the evaluation and recommendations about possible improvements of the whole education system in the organization

Intracortical microinjections may cause spreading depression and suppress absence seizures

Item does not contain fulltextIntracerebral microinjection is a commonly used technique for local delivery of biologically active agents. However, it is known that mechanical injury of the cortex can induce spreading depression (SD), a wave of transient cellular depolarization. We examined the effects of intracortical microinjections of a new selective I-h channel antagonist ORG 34167 and of different control treatments (saline and sham microinjections) on spontaneously occurring spike-wave discharges (SWDs) in WAG/Rij rats, a valid genetic model of absence epilepsy. Electroencephalographic (EEG) recording in awake rats has shown that both the drug and control microinjections are followed by long-term (for more than an hour) suppression of SWDs. dc-EEG recording in WAG/Rij rats has revealed that sham microinjections induce SD in 65% (31/48) cases. Number of SWDs decreased substantially for at least 90 min after the sham injections which induced cortical SD but remained unchanged if SD was not triggered by microinjection. These findings suggest that SD induced by intracortical microinjection may contribute to long-term suppression of non-convulsive epileptic activity after this experimental procedure

Coexistence of two types of nonconvulsive epilepsy in patients and genetic animal model (WAG/Rij rats) [in Russian]

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Understanding Spreading Depression from Headache to Sudden Unexpected Death

Spreading depression (SD) is a neurophysiological phenomenon characterized by abrupt changes in intracellular ion gradients and sustained depolarization of neurons. It leads to loss of electrical activity, changes in the synaptic architecture, and an altered vascular response. Although SD is often described as a unique phenomenon with homogeneous characteristics, it may be strongly affected by the particular triggering event and by genetic background. Furthermore, SD may contribute differently to the pathogenesis of widely heterogeneous clinical conditions. Indeed, clinical disorders related to SD vary in their presentation and severity, ranging from benign headache conditions (migraine syndromes) to severely disabling events, such as cerebral ischemia, or even death in people with epilepsy. Although the characteristics and mechanisms of SD have been dissected using a variety of approaches, ranging from cells to human models, this phenomenon remains only partially understood because of its complexity and the difficulty of obtaining direct experimental data. Currently, clinical monitoring of SD is limited to patients who require neurosurgical interventions and the placement of subdural electrode strips. Significantly, SD events recorded in humans display electrophysiological features that are essentially the same as those observed in animal models. Further research using existing and new experimental models of SD may allow a better understanding of its core mechanisms, and of their differences in different clinical conditions, fostering opportunities to identify and develop targeted therapies for SD-related disorders and their worst consequences