Linked Life Data

20834222

Source:http://linkedlifedata.com/resource/pubmed/id/20834222

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
43
pubmed:dateCreated
2010-9-13
pubmed:abstractText
Neurological injury is a frequent cause of morbidity and mortality from general anesthesia and related surgical procedures that could be alleviated by development of effective, easy to administer and safe preconditioning treatments. We seek to define the neural immune signaling responsible for cold-preconditioning as means to identify novel targets for therapeutics development to protect brain before injury onset. Low-level pro-inflammatory mediator signaling changes over time are essential for cold-preconditioning neuroprotection. This signaling is consistent with the basic tenets of physiological conditioning hormesis, which require that irritative stimuli reach a threshold magnitude with sufficient time for adaptation to the stimuli for protection to become evident. Accordingly, delineation of the immune signaling involved in cold-preconditioning neuroprotection requires that biological systems and experimental manipulations plus technical capacities are highly reproducible and sensitive. Our approach is to use hippocampal slice cultures as an in vitro model that closely reflects their in vivo counterparts with multi-synaptic neural networks influenced by mature and quiescent macroglia/microglia. This glial state is particularly important for microglia since they are the principal source of cytokines, which are operative in the femtomolar range. Also, slice cultures can be maintained in vitro for several weeks, which is sufficient time to evoke activating stimuli and assess adaptive responses. Finally, environmental conditions can be accurately controlled using slice cultures so that cytokine signaling of cold-preconditioning can be measured, mimicked, and modulated to dissect the critical node aspects. Cytokine signaling system analyses require the use of sensitive and reproducible multiplexed techniques. We use quantitative PCR for TNF-? to screen for microglial activation followed by quantitative real-time qPCR array screening to assess tissue-wide cytokine changes. The latter is a most sensitive and reproducible means to measure multiple cytokine system signaling changes simultaneously. Significant changes are confirmed with targeted qPCR and then protein detection. We probe for tissue-based cytokine protein changes using multiplexed microsphere flow cytometric assays using Luminex technology. Cell-specific cytokine production is determined with double-label immunohistochemistry. Taken together, this brain tissue preparation and style of use, coupled to the suggested investigative strategies, may be an optimal approach for identifying potential targets for the development of novel therapeutics that could mimic the advantages of cold-preconditioning.
pubmed:grant
pubmed:commentsCorrections
http://linkedlifedata.com/resource/pubmed/commentcorrection/20834222-11069581, http://linkedlifedata.com/resource/pubmed/commentcorrection/20834222-11180514, http://linkedlifedata.com/resource/pubmed/commentcorrection/20834222-11328886, http://linkedlifedata.com/resource/pubmed/commentcorrection/20834222-11910117, http://linkedlifedata.com/resource/pubmed/commentcorrection/20834222-12195028, http://linkedlifedata.com/resource/pubmed/commentcorrection/20834222-12379901, http://linkedlifedata.com/resource/pubmed/commentcorrection/20834222-14751586, http://linkedlifedata.com/resource/pubmed/commentcorrection/20834222-15126049, http://linkedlifedata.com/resource/pubmed/commentcorrection/20834222-15132435, http://linkedlifedata.com/resource/pubmed/commentcorrection/20834222-15362713, http://linkedlifedata.com/resource/pubmed/commentcorrection/20834222-15788779, http://linkedlifedata.com/resource/pubmed/commentcorrection/20834222-15829647, http://linkedlifedata.com/resource/pubmed/commentcorrection/20834222-16547515, http://linkedlifedata.com/resource/pubmed/commentcorrection/20834222-17459441, http://linkedlifedata.com/resource/pubmed/commentcorrection/20834222-18269679, http://linkedlifedata.com/resource/pubmed/commentcorrection/20834222-18270363, http://linkedlifedata.com/resource/pubmed/commentcorrection/20834222-18480142, http://linkedlifedata.com/resource/pubmed/commentcorrection/20834222-18615310, http://linkedlifedata.com/resource/pubmed/commentcorrection/20834222-18716210, http://linkedlifedata.com/resource/pubmed/commentcorrection/20834222-19020014, http://linkedlifedata.com/resource/pubmed/commentcorrection/20834222-19193879, http://linkedlifedata.com/resource/pubmed/commentcorrection/20834222-7608344, http://linkedlifedata.com/resource/pubmed/commentcorrection/20834222-8723705, http://linkedlifedata.com/resource/pubmed/commentcorrection/20834222-8956110, http://linkedlifedata.com/resource/pubmed/commentcorrection/20834222-8978384, http://linkedlifedata.com/resource/pubmed/commentcorrection/20834222-9547248, http://linkedlifedata.com/resource/pubmed/commentcorrection/20834222-9603200, http://linkedlifedata.com/resource/pubmed/commentcorrection/20834222-9930728
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
1940-087X
pubmed:author
pubmed:issnType
Electronic
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed:year
2010
pubmed:articleTitle
Strategies for study of neuroprotection from cold-preconditioning.
pubmed:affiliation
Department of Neurology, The University of Chicago Medical Center, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural, Video-Audio Media