Nitric Oxide and the Central Nervous System

During the last ten years, several investigators have reported that biological effects of endothelium-derived relaxing factor (EDRF; Furchgott and Zawadzki, 1980) are actually activities of a signal molecule, nitric oxide (NO; Moncada el al., 1988). This molecule is synthesised by endothelial vascular cells (Palmer el al., 1987, 1988; Ignarro, 1990). Endogenous NO is involved in many biological processes. The horseshoe crab (Lilllulus polypherus), that exists for 500 million years, synthesises NO from L-arginine to avoid aggregation of its circulating haemocytes (Radomski el al., 1991), wltile the blood sucking insect Rhodnius prolixus uses NO in its prey for vasodilatation and platelet anti-aggregation (Ribeiro el al., 1993). The goldfish Carassius auralus (Bruning el al., 1995) and the frog Xenopus laevis (Bruning and Mayer, 1996) use NO as a molecule for neuronal signalling. Evidence has accumulated that endogenous NO regulates not only mammalian blood vessels but many other systems (Moncada and Higgs, 1991). Almost every mammalian cell/system is under influence of NO, involving endotheliumMdependent relaxation (Furchgott and Zawadzki, 1980), neurotransmission (Garthwaite el al., 1988; Gillespie el al., 1989) and cell-mediated ilmllune response (Nathan and Hibbs, 1991). Appropriately, NO was proclaimed as a Molecule ojlhe Year for 1992 by the journal Science (Koshland, 1992). In addition, the beneficial effects of glyceryl trinitrate in coronary heart disease, known since 1867, have been recently explained through NO (Anggard, 1994). Alfred Nobel, who invented nitroglycerine. used the drug himself to relieve his coronary heart problems (Snyder and Bredt, 1992; HOlscher el al., 1995). Recently, it has been found that NO can exert not only cytoprotective but also cytotoxic effects in mammalian cells (Snyder and Bredt, 1992; Krencke el al., 1997). Moreover, it has been demonstrated that clarification of the dual effect of NO might have implications for clinical medicine with therapeutic opportunities (Snyder, 1993; Schmidt and \\Valter, 1994; Vallance and Moncada, 1994). Thus, the main goal of this thesis is to highlight the importance of this molecule, particularly in the neuropharmacology

7-Nitro indazole, an inhibitor of neuronal nitric oxide synthase, attenuates pilocarpine-induced seizures

7-Nitro indazole (25–100 mg/kg i.p.), an inhibitor of neuronal nitric oxide (NO) synthase, attenuated the severity of pilocarpine (300 mg/kg i.p.)-induced seizures in mice. This indicates that the decreased neuroexcitability of the central nervous system (CNS) following administration of 7-nitro indazole may be due to inhibition of neuronal NO synthase, implying that NO acts as an excitatory and proconvulsant factor in the CNS

Uticaj pentobarbitala i pentilenetetrazola na nivo azot oksida u frontalnom korteksu pacova

Levels of nitric oxide (NO) in the rats frontal cortex were continuously monitored before and after intraperitoneal administration of an antiepileptic drug-pentobarbital (20 and 40 mg/kg) or convulsant drug - pentylenetetrazol (50 mg/kg). Pentobarbital decreased the levels of NO in a dose dependent manner However, NO levels had a tendency to increase following the administration of pentylenetetrazol. It is suggested that central NO participates in the modulation of neuronal excitability, supporting the idea that NO is an important excitatory factor involved in the regulation of seizure susceptibility. Also, our results on anaesthetized rats suggests that endogenous NO may be involved in the mechanism of action of antiepileptic and analeptic drugs and this further suggest that NO levels in the human brain may decrease during antiepileptic therapy and increase during epileptic attacks or administration of excitatory drugs. The aim of the present study was to determine the possible role of NO levels in the brain during neuronal excitability and seizures.Nivo azot oksida (NO) u frontalnom korteksu pacova meren je kontinuirano kako pre, tako i nakon intraperitonealne primene antiepileptika pentobarbitala (u dozi od 20 i 40 mg/kg) ili konvulzivnog agensa pentilenetetrazola (u dozi od 50 mg/kg). Rezultati ovih eksperimenta su ukazali da pentobarbital smanjuje nivo NO u frontalnom korteksu pacova, dok koncentracija NO ima tendeciju rasta nakon primene pentilenetetrazola. Osim toga, dokazano je da endogeni NO ima važnu ekscitatornu ulogu u centralnim mehanizmima nastanka epilepsije. Takođe, naši rezultati su ukazali da kod anestetisanih životinja endogeni nivo NO ima uticaja na dejstvo kako antikonvulzivnih, tako i prokonvulzivnih lekova. Nivo NO u mozgu pacova je bio snižen tokom terapije antiepilepticima, a povišen tokom epileptičkih napada ili primene lekova iz grupe centralnih stimulansa

Genetics of Menstrual Migraine: The Epidemiological Evidence

Approximately one of every three to five women with migraine without aura experience migraine attacks in relation to menstruation. The International Classification of Headache Disorders, 2nd Edition provides appendix diagnoses for pure and menstrually related migraine without aura that need further validation. Probands with menstrual migraine might have more affected relatives than probands with nonmenstrual migraine. However, precise epidemiological, family, and twin data still are lacking

Migraine in women: the role of hormones and their impact on vascular diseases

Migraine is a predominantly female disorder. Menarche, menstruation, pregnancy, and menopause, and also the use of hormonal contraceptives and hormone replacement treatment may influence migraine occurrence. Migraine usually starts after menarche, occurs more frequently in the days just before or during menstruation, and ameliorates during pregnancy and menopause. Those variations are mediated by fluctuation of estrogen levels through their influence on cellular excitability or cerebral vasculature. Moreover, administration of exogenous hormones may cause worsening of migraine as may expose migrainous women to an increased risk of vascular disease. In fact, migraine with aura represents a risk factor for stroke, cardiac disease, and vascular mortality. Studies have shown that administration of combined oral contraceptives to migraineurs may further increase the risk for ischemic stroke. Consequently, in women suffering from migraine with aura caution should be deserved when prescribing combined oral contraceptives