Lipopolysaccharide induced increase in seizure activity in two animal models of absence epilepsy WAG/Rij and GAERS rats and Long Evans rats

We showed previously that the number and time of spike-wave discharges (SWDs) were increased after intraperitoneal (i.p.) injection of lipopolysaccharide (LPS), an effect, which was completely abolished by cyclooxygenase-2 (COX-2) inhibitor indomethacin (IND) pretreatment in Wistar Albino Glaxo/Rijswijk (WAG/Rij) rats. These and other results suggest that injection of LPS to genetically absence epileptic animals, such as WAG/Rij rats, may allow us to investigate relationships between absence epilepsy and LPS evoked neuroinflammation processes. However, LPS may evoke different effects on absence epileptic activity in various animal strains. Thus, to extend our previous results, we injected two doses of LPS (50 μg/kg and 350 μg/kg i.p.) alone and in combination with IND (10mg/kg IND i.p. +50 μg/kg LPS) into rats of two model animal strains (WAG/Rij rats; GAERS rats: Genetic Absence Epileptic Rats from Strasbourg) and into Long Evans rats. The effects of treatments on SWD number and SWD duration were examined. Both doses of LPS increased the SWD number and the total time of SWDs dose-dependently during the whole 4-h recording period, which was abolished by IND pretreatment in all three investigated strains. These results extend our previous results suggesting that our methods using LPS injection into freely moving absence epileptic rats is applicable not only in well-established animal models of absence epilepsy such as WAG/Rij rats and GAERS rats but also in Long Evans rats to investigate links between inflammation and absence epilepsy

5'-nucleotidases, nucleosides and their distribution in the brain: pathological and therapeutic implications

Elements of the nucleoside system (nucleoside levels, 5'-nucleotidases (5'NTs) and other nucleoside metabolic enzymes, nucleoside transporters and nucleoside receptors) are unevenly distributed in the brain, suggesting that nucleosides have region-specific functions in the human brain. Indeed, adenosine (Ado) and non-Ado nucleosides, such as guanosine (Guo), inosine (Ino) and uridine (Urd), modulate both physiological and pathophysiological processes in the brain, such as sleep, pain, memory, depression, schizophrenia, epilepsy, Huntington's disease, Alzheimer's disease and Parkinson's disease. Interactions have been demonstrated in the nucleoside system between nucleoside levels and the activities of nucleoside metabolic enzymes, nucleoside transporters and Ado receptors in the human brain. Alterations in the nucleoside system may induce pathological changes, resulting in central nervous system (CNS) diseases. Moreover, several CNS diseases such as epilepsy may be treated by modulation of the nucleoside system, which is best achieved by modulating 5'NTs, as 'NTs exhibit numerous functions in the CNS, including intracellular and extracellular formation of nucleosides, termination of nucleoside triphosphate signaling, cell adhesion, synaptogenesis and cell proliferation. Thus, modulation of 5'NT activity may be a promising new therapeutic tool for treating several CNS diseases. The present article describes the regionally different activities of the nucleoside system, demonstrates the associations between these activities and 5'NT activity and discusses the therapeutic implications of these associations

Dehydroepiandrosterone sulfate (DHEAS) is neuroprotective when administered either before or after injury in a focal cortical cold lesion model

Dehydroepiandrosterone and its sulfate (DHEAS) are sex hormone precursors that exert marked neurotrophic and/or neuroprotective activity in the central nervous system. The present study evaluated the effects of DHEAS and 17�-estradiol (E2) in a focal cortical cold lesion model, in which DHEAS (50 mg/kg, sc) and E2 (35 mg/kg, sc) were administered either as pretreatment (two subsequent injections 1 d and 1 h before lesion induction) or posttreatment (immediately after lesion induction). The focal cortical cold lesion was induced in the primary motor cortex by means of a cooled copper cylinder placed directly onto the cortical surface. One hour later, the animals were killed, the brains cut into 0.4-mm-thick slices, and the sections stained with 1% triphenyltetrazolium chloride. The volume of the hemispheric lesion was calculated for each animal. The results demonstrated that the lesion area was significantly attenuated in both the DHEAS- and E2- preand posttreated groups and that in the presence of letrozole, a nonsteroidal aromatase inhibitor, no neuroprotection was observed, suggesting that the beneficial effect of DHEAS on the cold injury might depend on the conversion of DHEAS to E2 within the brain. It is concluded that even a single posttraumatic administration of DHEAS may be of substantial therapeutic benefit in the treatment of focal brain injury with vasogenic edema

Iszkémia/reperfúzió indukálta károsodás: aritmiák és szívfunkciók farmakológiai befolyásolása, molekuláris mechanizmusok. = Ischemia/reperfusion induced cardiac injury: mechanisms and pharmacology

A halálozási statisztikákat évek óta a szív- és érrendszeri megbetegedések vezetik. A minőségi élet megteremtéséhez szükséges a korai halálozás okainak visszaszorítása, a megelőzés szerepének növelése. A betegségcsoport népegészségügyi jelentőségére való tekintettel minden új diagnosztikai és terápiás eljárás komoly tudományos és jelentős piaci érdeklődésre is számot tarthat. A szívizom iszkémiás megbetegedéseiben és a szívsebészeti beavatkozások során az iszkémia/reperfúzió jelenségének központi szerepe van. A hosszabb ideig tartó myocardiális iszkémia szívelégtelenséghez és sejthalálhoz vezethet. A korai terápia (reperfúzió) célja az iszkémiás terület oxigénnel és tápanyaggal történő ellátása, a keringés újraindítása. Bár a reperfúzió nélkülözhetetlen az iszkémia által károsodott szervek felépülésében, mégsem kockázatmentes, mivel maga a reperfúzió súlyosbíthatja az iszkémia utáni állapotban lévő szövetek funkcióját. Az iszkémiás szívbetegség leggyakoribb következményei az angina pectoris, szívinfarktus, szívelégtelenség és az aritmiák következtébenfellépő hirtelen szívhalál. Kísérleteinkben az iszkémia/reperfúzió-indukálta károsodások molekuláris mechanizmusait és farmakológiai befolyásolási lehetőségeit vizsgáltuk. Eredményeinket több hazai és nemzetközi konferencián mutattuk be, valamint számos nemzetközi folyóiratban publikáltuk, mely közlemények 2 db Ph.D. dolgozat alapját képezték. Kutatási eredményeinkből két hazai és két nemzetközi szabadalmi bejelentést tettünk. | Cardiovascular disorders are the leading cause of death worldwide. It is very important to increase the role of prevention in order to decrease the early death. Because of the epidemiological significance of the cardiovascular disorders every new diagnostic and therapeutic approach will have high interest both in science and in the pharmaceutical industry. Ischemia/reperfusion has a crucial role in ischemic heart diseases and cardiac surgery. Decreased oxygen supply and perfusion can cause serious injuries. The aim of the early therapy is the restoration of blood flow into the myocardium. However, reperfusion is necessary for the recovery it is not without hazard, because it can cause cell death. The most frequent consequences of ischemic heart disease are angina pectoris, infarction, heart failure and sudden cardiac death caused by arrhythmias. The overall aims of our studies were to investigate the molecular mechanisms of ischemia/reperfusion-induced cardiovascular damages and to develop new pharmacological approaches capable of reducing ischemia/reperfusion-induced damage. Our results allow us the more precise cognition of the mechanisms of ischemia/reperfusion and arrhythmias, making the possibility the development of new drugs. The results of our experiments were introduced on national and international conferences and published in international journals. Two Ph.D. dissertations were made from our results and we have 2 Hungarian and 2 international patents also