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Acute Maternal Oxidant Exposure Causes Susceptibility Of The Fetal Brain To Inflammation And Oxidative Stress, Feroz Akhtar, Christopher A. Rouse, Gabriel Catano, Marcus Montalvo, Sarah L. Ullevig, Reto Asmis, Kusum K. Kharbanda, Shivani K. Maffi
Acute Maternal Oxidant Exposure Causes Susceptibility Of The Fetal Brain To Inflammation And Oxidative Stress, Feroz Akhtar, Christopher A. Rouse, Gabriel Catano, Marcus Montalvo, Sarah L. Ullevig, Reto Asmis, Kusum K. Kharbanda, Shivani K. Maffi
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Background: Maternal exposure to environmental stressors poses a risk to fetal development. Oxidative stress (OS), microglia activation, and inflammation are three tightly linked mechanisms that emerge as a causal factor of neurodevelopmental anomalies associated with prenatal ethanol exposure. Antioxidants such as glutathione (GSH) and CuZnSOD are perturbed, and their manipulation provides evidence for neuroprotection. However, the cellular and molecular effects of GSH alteration in utero on fetal microglia activation and inflammation remain elusive.
Methods: Ethanol (EtOH) (2.5 g/kg) was administered to pregnant mice at gestational days 16–17. One hour prior to ethanol treatment, N-acetylcysteine (NAC) and L-buthionine sulfoximine (BSO) …
Deficiency Of Tnf Receptors Suppresses Microglial Activation And Alters The Susceptibility Of Brain Regions To Mptp-Induced Neurotoxicity: Role Of Tnf-Α, Krishnan Sriram, Joanna M. Matheson, Stanley A. Benkovic, Diane B. Miller, Michael I. Luster, James P. O'Callaghan
Deficiency Of Tnf Receptors Suppresses Microglial Activation And Alters The Susceptibility Of Brain Regions To Mptp-Induced Neurotoxicity: Role Of Tnf-Α, Krishnan Sriram, Joanna M. Matheson, Stanley A. Benkovic, Diane B. Miller, Michael I. Luster, James P. O'Callaghan
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Enhanced expression of tumor necrosis
factor (TNF) -α, is associated with the neuropathological
effects underlying disease-, trauma- and chemically
induced neurodegeneration. Previously, we have shown
that deficiency of TNF receptors protects against
MPTP-induced striatal dopaminergic neurotoxicity,
findings suggestive of a role for TNF-α in neurodegeneration.
Here, we demonstrate that deficiency of TNF
receptors suppresses microglial activation and alters
the susceptibility of brain regions to MPTP. MPTPinduced
expression of microglia-derived factors,
TNF-α, MCP-1, and IL-1α, preceded the degeneration
of striatal dopaminergic nerve terminals and astrogliosis,
as assessed by loss of striatal dopamine and TH, …