Imbalance of the excitatory neurotransmitter glutamate and of the inhibitory neurotransmitter GABA is one of several causes of seizures. ATP has also been implicated in epilepsy. However, little is known about the mechanisms involved in the release of ATP from cells and the consequences of the altered ATP signaling during seizures. Pannexin1 (Panx1) is found in astrocytes and in neurons at high levels in the embryonic and young postnatal brain, declining in adulthood. Panx1 forms large-conductance voltage sensitive plasma membrane channels permeable to ATP that are also activated by elevated extracellular K+ and following P2 receptor stimulation. Based on these properties, we hypothesized that Panx1 channels may contribute to seizures by increasing the levels of extracellular ATP. Using pharmacological tools and two transgenic mice deficient for Panx1 we show here that interference with Panx1 ameliorates the outcome and shortens the duration of kainic acid-induced status epilepticus. These data thus indicate that the activation of Panx1 in juvenile mouse hippocampi contributes to neuronal hyperactivity in seizures.

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Despite certain limitations, our new model correlates well with current infantile spasm hypotheses and opens an opportunity for development and testing of new effective drugs.

An 8-month multicentre prospective randomized study aimed at comparing the effects of dopamine receptor agonists pramipexole (PPX; Mirapexin) and pergolide (PRG; Permax) as add-on to L-dopa therapy on depression [Montgomery and Asberg Depression Rating Scale (MADRS)] in 41 non-demented patients (25 men, 16 women) suffering from both mild or moderate depression and advanced Parkinson's disease (PD). The assessment was performed by a blinded independent observer. Motor symptoms (UPDRS III), motor complications (UPDRS IV), activities of daily living (UPDRS II and VI) and depressive symptoms as measured by Self - Rating Depression Scale by Zung were evaluated in an open-label design. The average value of Zung scores decreased significantly in both groups with no statistical difference between both groups. A significant decrease in the average value of MADRS scores was present only in the PPX group. The average UPDRS scores decreased significantly with no statistical difference between both groups at the comparable average total daily dose of both preparations. In both cases, the total daily dose of L-dopa decreased significantly but the decrease was statistically more pronounced in the PRG group. Our results demonstrate the antidepressant effect of PPX in patients with PD while we can't make any conclusions with regard to antidepressant effect of PRG.

Summary: Purpose:We investigated the activation of microglia and astrocytes, induction of cytokines, and hippocampal neuronal damage, 4 and 24 h after kainic acid-induced status epilepticus (SE) in postnatal day (PN) 9, 15, and 21 rats.Methods: Limbic seizures were induced by systemic injection of kainic acid. Glia activation and neuronal cell loss were studied by using immunocytochemistry and Western blot. Cytokine expression was analyzed by reverse transcriptasepolymerase chain reaction (RT-PCR) followed by Southern blot quantification.Results: After SE onset, hippocampal glia activation, cytokine expression, and neuronal damage are all age-dependent phenomena. In the hippocampus, neuronal injury occurs only when cytokines are induced in glia, and cytokine synthesis precedes the appearance of degenerating neurons. Neuronal injury is more pronounced when interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) are produced in addition to .Conclusions: This study shows that cytokine induction in rat brain after sustained seizures is age dependent, and it is associated with the appearance of cell injury. Key Words: Brain development-Interleukins-Neurodegeneration-Hippocampus-Seizures-Rat.Proinflammatory cytokines and related inflammatory and antiinflammatory molecules are rapidly overexpressed by glia in adult rodent hippocampus in various models of limbic seizures (1-3). In the adult brain, cytokines are expressed to a larger extent when seizures are associated with neuronal damage, suggesting a link between cytokine production and the occurrence of neuronal injury (1,4). Thus it has been shown that in mature rat brain, proinflammatory cytokines, and in particular interleukin (IL)-1β, act as modulators of various forms of neurodegeneration (5-7).In humans and in experimental models of epilepsy, seizure susceptibility and the associated neuronal damage are age-dependent phenomena, changing dramatically during postnatal development. In the first 2 postnatal weeks, the brain is more prone to seizure activity, but it is relatively resistant to irreversibile seizure-induced damage as compared with adult brain (8-12).The factors implicated in the occurrence of agedependent seizure-related injury are still unclear. We