Neuroprotective role of minocycline in co-cultures of human fetal neurons and microglia.
ABSTRACT Bacterial infections during pregnancy often result in premature birth and neonatal white matter damage. During these infections, microglia, the resident immune cells of the CNS, undergo activation and contribute to further neuronal damage of the CNS. Minocycline, a second-generation tetracycline antibiotic, inhibits microglial activation and protects neurons in rodents but data about its effects on human cells are limited. We studied the mechanism of the neuroprotective effect of minocycline in either purified cell cultures or co-cultures of microglia and neurons from human fetal brain during inflammation induced by lipopolysaccharide (LPS). In neuron/microglial co-cultures, minocycline treatment prevented activation and proliferation of microglia and protected neurons as demonstrated by decreased neuronal cell death and a shift of Bcl-2 family proteins toward anti-apoptotic ratio. Notably, neither minocycline nor LPS had an effect on neurons in purified neuronal cultures. The ability of minocycline to regulate activation of human fetal microglia might be relevant in therapies used towards treating neonatal CNS infections.
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ABSTRACT: Although the role of microglial activation in neural injury remains controversial, there is increasing evidence for a detrimental effect in the immature brain, which may occur in response to release of neurotoxic substances including pro-inflammatory cytokines. However, the signaling mechanisms involved in microglial-induced neuronal cell death are unclear. Microglia isolated from the brains of wild-type (WT) or MyD88 knockout (KO) mice were exposed to PBS or the TLR4-ligand LPS (100 ng/mL) for 2, 6, 14, or 24 h, and the microglia-conditioned medium (MCM) collected. Detection of multiple inflammatory molecules in MCM was performed using a mouse 22-plex cytokine microbead array kit. Primary neuronal cultures were supplemented with the 14 or 24 h MCM, and the degree of neuronal apoptosis examined after exposure for 24 h. Results showed a rapid and sustained elevation in multiple inflammatory mediators in the MCM of WT microglia exposed to LPS, which was largely inhibited in MyD88 KO microglia. There was a significant increase in apoptotic death measured at 24 h in cultured neurons exposed to CM from either 14 or 24 h LPS-stimulated WT microglia (p<.05 vs. WT control). By contrast, there was no increase in apoptotic death in cultured neurons exposed to CM from 14 or 24 h LPS-stimulated MyD88 KO microglia (p=.15 vs. MyD88 KO control). These data suggest that MyD88-dependent activation of microglia by LPS causes release of factors directly toxic to neurons.Brain Behavior and Immunity 11/2009; 24(5):776-83. DOI:10.1016/j.bbi.2009.10.018 · 6.13 Impact Factor
Conference Paper: 1.8 TeV Tevatron upgrade lattices[Show abstract] [Hide abstract]
ABSTRACT: The present Fermilab upgrade program calls for a future higher-energy (⩾1.5 TeV) superconducting accelerator to reside in the existing Tevatron tunnel. Three possible lattice designs for this accelerator are presented. The first involves longer straight sections which permit the extraction of 1.8-TeV beams to the fixed target experimental areas or external aborts. The second option uses stronger focusing quadrupoles to reduce the beam size throughout the accelerator. In this scheme, a large number of quadrupole circuits provide the necessary matching of the dispersion function across the long straight sections. The third option uses longer standard cells in the arcs, and the cell length is strategically chosen to minimize the dispersion wave generated by the medium- and mini-straight sections located in the arcs. The beam size is not as small as in the second option, though it is better behaved than in the present Tevatron lattice; in addition, it is believed that separator and low-beta schemes can be more easily implemented using this lattice designParticle Accelerator Conference, 1989. Accelerator Science and Technology., Proceedings of the 1989 IEEE; 04/1989
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ABSTRACT: In this paper, we propose a new design , which utilizes "empty squares" or narrow squares or narrow rings as the basic element for the fabrication of hard layer of MRAM. At remanence a stable bi-domain state called the "onion" state is observed. The onion state corresponds to each half of the square ring, on either side of the diagonal, having the same magnetization orientation and forming head-to-head and tail-to-tail domain walls.