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• W2699697708 startingPage "6877" @default.
• W2699697708 abstract "Cytomegalovirus (CMV) is the most common infectious cause of brain defects and neurological dysfunction in developing human babies. Due to the teratogenicity and toxicity of available CMV antiviral agents, treatment options during early development are markedly limited. Valnoctamide (VCD), a neuroactive mood stabilizer with no known teratogenic activity, was recently demonstrated to have anti-CMV potential. However, it is not known whether this can be translated into an efficacious therapeutic effect to improve CMV-induced adverse neurological outcomes. Using multiple models of CMV infection in the developing mouse brain, we show that subcutaneous low-dose VCD suppresses CMV by reducing the level of virus available for entry into the brain and by acting directly within the brain to block virus replication and dispersal. VCD during the first 3 weeks of life restored timely acquisition of neurological milestones in neonatal male and female mice and rescued long-term motor and behavioral outcomes in juvenile male mice. CMV-mediated brain defects, including decreased brain size, cerebellar hypoplasia, and neuronal loss, were substantially attenuated by VCD. No adverse side effects on neurodevelopment of uninfected control mice receiving VCD were detected. Treatment of CMV-infected human fetal astrocytes with VCD reduced both viral infectivity and replication by blocking viral particle attachment to the cell, a mechanism that differs from available anti-CMV drugs. These data suggest that VCD during critical periods of neurodevelopment can effectively suppress CMV replication in the brain and safely improve both immediate and long-term neurological outcomes.SIGNIFICANCE STATEMENT Cytomegalovirus (CMV) can irreversibly damage the developing brain. No anti-CMV drugs are available for use during fetal development, and treatment during the neonatal period has substantial limitations. We studied the anti-CMV actions of valnoctamide (VCD), a psychiatric sedative that appears to lack teratogenicity and toxicity, in the newborn mouse brain, a developmental period that parallels that of an early second-trimester human fetus. In infected mice, subcutaneous VCD reaches the brain and suppresses viral replication within the CNS, rescuing the animals from CMV-induced brain defects and neurological problems. Treatment of uninfected control animals exerts no detectable adverse effects. VCD also blocks CMV replication in human fetal brain cells." @default.
• W2699697708 created "2017-06-30" @default.
• W2699697708 creator A5004172478 @default.
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• W2699697708 creator A5048079403 @default.
• W2699697708 creator A5079441146 @default.
• W2699697708 creator A5086903244 @default.
• W2699697708 date "2017-06-19" @default.
• W2699697708 modified "2023-10-15" @default.
• W2699697708 title "Valnoctamide Inhibits Cytomegalovirus Infection in Developing Brain and Attenuates Neurobehavioral Dysfunctions and Brain Abnormalities" @default.
• W2699697708 cites W1481250329 @default.
• W2699697708 cites W1503832746 @default.
• W2699697708 cites W1516408025 @default.
• W2699697708 cites W1533329967 @default.
• W2699697708 cites W1556397944 @default.
• W2699697708 cites W1575495719 @default.
• W2699697708 cites W1582110922 @default.
• W2699697708 cites W1595963262 @default.
• W2699697708 cites W1600270952 @default.
• W2699697708 cites W1649304867 @default.
• W2699697708 cites W1655649919 @default.
• W2699697708 cites W1923715812 @default.
• W2699697708 cites W1938649346 @default.
• W2699697708 cites W1964994687 @default.
• W2699697708 cites W1965167705 @default.
• W2699697708 cites W1970229951 @default.
• W2699697708 cites W1980388563 @default.
• W2699697708 cites W1987373707 @default.
• W2699697708 cites W1996509490 @default.
• W2699697708 cites W1998041902 @default.
• W2699697708 cites W1999277080 @default.
• W2699697708 cites W2000405418 @default.
• W2699697708 cites W2004360037 @default.
• W2699697708 cites W2007434627 @default.
• W2699697708 cites W2008554212 @default.
• W2699697708 cites W2009740169 @default.
• W2699697708 cites W2011301739 @default.
• W2699697708 cites W2012427126 @default.
• W2699697708 cites W2014520750 @default.
• W2699697708 cites W2014634372 @default.
• W2699697708 cites W2018369464 @default.
• W2699697708 cites W2022567100 @default.
• W2699697708 cites W2023013517 @default.
• W2699697708 cites W2024454437 @default.
• W2699697708 cites W2024505394 @default.
• W2699697708 cites W2027713233 @default.
• W2699697708 cites W2027917639 @default.
• W2699697708 cites W2036915869 @default.
• W2699697708 cites W2041040744 @default.
• W2699697708 cites W2041554454 @default.
• W2699697708 cites W2042129729 @default.
• W2699697708 cites W2044488698 @default.
• W2699697708 cites W2045598092 @default.
• W2699697708 cites W2046087859 @default.
• W2699697708 cites W2049867157 @default.
• W2699697708 cites W2053909439 @default.
• W2699697708 cites W2054894217 @default.
• W2699697708 cites W2056610335 @default.
• W2699697708 cites W2056774192 @default.
• W2699697708 cites W2066440126 @default.
• W2699697708 cites W2076566560 @default.
• W2699697708 cites W2081325732 @default.
• W2699697708 cites W2090660498 @default.
• W2699697708 cites W2092396621 @default.
• W2699697708 cites W2095826033 @default.
• W2699697708 cites W2097655460 @default.
• W2699697708 cites W2097711239 @default.
• W2699697708 cites W2098816998 @default.
• W2699697708 cites W2100336836 @default.
• W2699697708 cites W2100876024 @default.
• W2699697708 cites W2101704740 @default.
• W2699697708 cites W2108367007 @default.
• W2699697708 cites W2120426862 @default.
• W2699697708 cites W2129626981 @default.
• W2699697708 cites W2133410219 @default.
• W2699697708 cites W2133963802 @default.
• W2699697708 cites W2138286114 @default.
• W2699697708 cites W2142161841 @default.
• W2699697708 cites W2143217444 @default.
• W2699697708 cites W2144641135 @default.
• W2699697708 cites W2149329811 @default.
• W2699697708 cites W2153617971 @default.
• W2699697708 cites W2155471406 @default.
• W2699697708 cites W2159030941 @default.
• W2699697708 cites W2159934585 @default.
• W2699697708 cites W2160800714 @default.
• W2699697708 cites W2161092010 @default.
• W2699697708 cites W2162843814 @default.
• W2699697708 cites W2214734933 @default.
• W2699697708 cites W2341341271 @default.
• W2699697708 cites W2395719560 @default.
• W2699697708 cites W2398158375 @default.
• W2699697708 cites W2403265895 @default.
• W2699697708 cites W2419119573 @default.
• W2699697708 cites W2461122983 @default.
• W2699697708 cites W2461289608 @default.
• W2699697708 cites W2509248929 @default.

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