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Ischemia-associated oxidative damage leading to necrosis is a major cause of catastrophic tissue loss, and elucidating its signaling mechanism is therefore of paramount importance. p53 is a central stress sensor responding to multiple insults, including oxidative stress to orchestrate apoptotic and autophagic cell death. Whether p53 can also activate(More)
Ischemic stroke induces neuronal death in the core of the infarct within a few hours and the secondary damage in the surrounding regions over a long period of time. Reduction of inflammation using pharmacological reagents has become a target of research for the treatment of stroke. Cyclooxygenase 2 (COX-2), a marker of inflammation, is induced during stroke(More)
Microglia are the immunocompetent cells of the central nervous system. In the physiological setting, their highly motile processes continually survey the local brain parenchyma and transiently contact synaptic elements. Although recent work has shown that the interaction of microglia with synapses contributes to synaptic remodeling during development, the(More)
Synaptic plasticity is critical for elaboration and adaptation in the developing and developed brain. It is well established that astrocytes play an important role in the maintenance of what has been dubbed "the tripartite synapse". Increasing evidence shows that a fourth cell type, microglia, is critical to this maintenance as well. Microglia are the(More)
THE INFLAMMATION THAT ACCOMPANIES ACUTE INJURY HAS DUAL FUNCTIONS: bactericidal action and repair. Bactericidal functions protect damaged tissue from infection, and repair functions are initiated to aid in the recovery of damaged tissue. Brain injury is somewhat different from injuries in other tissues in two respects. First, many cases of brain injury are(More)
Glutamatergic neurons contain free zinc packaged into neurotransmitter-loaded synaptic vesicles. Upon neuronal activation, the vesicular contents are released into the synaptic space, whereby the zinc modulates activity of postsynaptic neurons though interactions with receptors, transporters and exchangers. However, high extracellular concentrations of zinc(More)
Microglia are active players in inflammation, but also have important supporting roles in CNS maintenance and function, including modulation of neuronal activity. We previously observed an increase in the frequency of excitatory postsynaptic current in organotypic brain slices after depletion of microglia using clodronate. Here, we describe that local(More)
2ϩ responses (Fluo4 fluorescence) in enteric neurons and enteric glia within a myenteric ganglion from the guinea pig distal colon. Ca 2ϩ responses were stimulated in enteric neurons with the nicotinic agonist epibatidine and in enteric glia with the purine ATP. For more information, see the article by Gulbransen et al. in this issue (pages 6801– 6809).
Epidemiological studies have reported that cigarette smoking increases the risk of developing multiple sclerosis (MS) and accelerates its progression. However, the molecular mechanisms underlying these effects remain unsettled. We have investigated here the effects of the nicotine and the non-nicotine components in cigarette smoke on MS using the(More)
Pr ecis: These results offer preclinical proof-of-concept for a mitotic kinase inhibitor as a new therapeutic for the most deadly type of brain cancer. Pr ecis: Molecular responses to aromatase inhibition are similar in lobular and ductal breast tumors, despite clear histologic differences before and after treatment, with implications for the use of(More)
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