Background/Aims: Multiple sclerosis (MS) is a prototypical autoimmune central nervous system (CNS) disease. Particularly progressive forms of MS (PMS) show significant neuroaxonal damage as consequence of demyelination and neuronal hyperexcitation. Immuno-modulatory treatment strategies are beneficial in relapsing MS (RMS), but mostly fail in PMS. Pregabalin (Lyrica®) is prescribed to MS patients to treat neuropathic pain. Mechanistically, it targets voltage-dependent Ca2+ channels and reduces harmful neuronal hyperexcitation in mouse epilepsy models. Studies suggest that GABA analogues like pregabalin exert neuroprotective effects in animal models of ischemia and trauma. Methods: We tested the impact of pregabalin in a mouse model of MS (experimental autoimmune encephalomyelitis, EAE) and performed histological and immunological evaluations as well as intravital two-photon-microscopy of brainstem EAE lesions. Results: Both prophylactic and therapeutic treatments ameliorated the clinical symptoms of EAE and reduced immune cell infiltration into the CNS. On neuronal level, pregabalin reduced long-term potentiation in hippocampal brain slices indicating an impact on mechanisms of learning and memory. In contrast, T cells, microglia and brain endothelial cells were unaffected by pregabalin. However, we found a direct impact of pregabalin on neurons during CNS inflammation as it reversed the pathological elevation of neuronal intracellular Ca2+ levels in EAE lesions. Conclusion: The presented data suggest that pregabalin primarily acts on neuronal Ca2+ channel trafficking thereby reducing Ca2+-mediated cytotoxicity and neuronal damage in an animal model of MS. Future clinical trials need to assess the benefit for neuronal survival by expanding the indication for pregabalin administration to MS patients in further disease phases.
From the time of fertilisation, human offspring are sensitive to environmental factors. 1,2 Toxic substances are the most influential factors for the development of the unborn child, 3 and alcohol and nicotine are increasingly being consumed during pregnancy. 3,4 Both substances pass directly through the placenta into the foetal blood circulation, causing toxic effects, for example on cell development. 4 In addition, the biochemically immature organism delays detoxification processes. 5 Hence, prenatal exposure to alcohol and nicotine is one of the highest risks for the course of a healthy pregnancy. Different consumption patterns, like high, moderate and low amounts of substances, may have distinct influences on early child development. 4 This review focused on the effects of low and moderate amounts of prenatal alcohol and nicotine exposure. The current literature lacks coherent definitions of
Since their market launch in 2007, e-cigarettes gained popularity and were considered a relatively safe alternative to traditional cigarettes. Pregnant women and women of childbearing age in particular are increasingly turning to e-cigarettes. Little is known about the effects of prenatal exposure on the affected foetus. This paper aims to provide an overview of the current research on the effects of prenatal e-cigarette exposure on the foetus. Since studies in humans are lacking to date, this review refers only to animal and in vitro analyses. The PubMed and Web of Science databases were used for an extensive literature search. The search yielded N = 17 significant research papers. Possible sequelae resulting from prenatal exposure to traditional cigarettes were also seen in prenatal exposure to e-cigarettes. Prenatal e-cigarette exposure was found to be associated with increased DNA methylation overall, resulting in lower gene expression. This could adversely impact the development of affected children, especially in case of those genes relevant to their development. In mice, for example, this greatly reduced the cell vitality of neural and stem cells and increased cell death. Further, prenatal exposure to e-cigarettes resulted in numerous developmental disorders, such as malformations of facial morphology and lower birth weight. Moreover, in animal models the animals suffered from a deterioration of their short-term memory. Activity and cognitive flexibility increased, while anxiety behaviour decreased. It is clear that more research and especially studies of humans are needed on this issue. In addition, there is a need for more intense education of prenatal care professionals as well as women of childbearing age and during pregnancy.
Aims: The consumption of alcohol and nicotine during pregnancy relate to a multitude of personal and socioeconomic factors. Since even the consumption in non-clinical populations pose a health risk to children, epidemiologic data related to factors potentially contributing to an increase in consumption during pregnancy were investigated. Methodology: Cross-sectional analyses were based on interview data from 260 pregnant women taking part in a longitudinal intervention project (Bremer Initiative to Foster Early Child Development). Women had a below-average family income, a migration background, or faced other social and cultural challenges. Descriptive statistics were calculated to determine consumption prevalence. Logistic regression models were conducted to estimate associations of alcohol or nicotine consumption with personal and socioeconomic factors. Results: Of the total sample (mean age: 31.1 years), 45 % consumed alcohol and/or nicotine during pregnancy. 92.3 % quit drinking and 62.8 % stopped smoking following confirmation of pregnancy. Better social support and higher age increased the likelihood of alcohol consumption, while this was decreased by an Islamic cultural background. Smoking was predicted by a lower level of education. Unplanned pregnancies predicted the consumption of both, alcohol and nicotine. Conclusions: A multitude of factors influence alcohol and nicotine consumption in non-clinical populations. Preventive strategies should include pre-pregnancy stages and health information needs to mirror factors contributing to consumption.
Zusammenfassung. Kinder sind bereits im Mutterleib sensitiv für Umwelteinflüsse. Pränataler Alkoholkonsum zählt dabei zu den einflussreichsten Risikofaktoren für die frühkindliche Entwicklung. Das Ziel ist es, einen Überblick über die aktuelle Forschungslage zum Thema Alkoholkonsum während der Schwangerschaft zu geben. Darüber hinaus wird der Forschungsstand zu Belastungen und Folgeschäden für die frühkindliche Entwicklung durch pränatale Alkoholexposition, aber auch zu weiteren Risikofaktoren zusammengefasst. Es wird gezeigt, dass das Wissen um die Prävalenz für Alkoholkonsum während der Schwangerschaft sowohl für die Erforschung der Folgen als auch für das Umsetzen von präventiven Maßnahmen ausschlaggebend ist. Die Prävalenzen unterscheiden sich nicht nur regional, sondern können auch durch andere Faktoren beeinflusst werden. Es wird deutlich, dass der Risikofaktor Alkohol und dessen mögliche Auswirkungen auf die frühkindliche Entwicklung nicht isoliert, sondern in Abhängigkeit von weiteren genetischen und Umweltfaktoren betrachtet werden müssen. Denn auch Folgen von weiteren perinatalen Risikofaktoren machen sich in den ersten beiden Lebensjahren bemerkbar. Beispiele für Entwicklungsstörungen in dieser Entwicklungsspanne sind externalisierendes Verhalten und kognitive Beeinträchtigungen. Inwieweit sich perinatale Risikofaktoren jedoch auf Entwicklungsverläufe von Kindern, die durch pränatalen Alkoholkonsum belastet sind, auswirken, erfasst eine umfassende Diskussion. Diese Lücke gilt es zu schließen um das Zusammenspiel perinataler Risiken genauer zu verstehen und adäquat entgegenwirken zu können.
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