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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
11
pubmed:dateCreated
2005-10-25
pubmed:abstractText
Previously, we identified proteins released from degenerating cultured cortical neurons as novel cerebrospinal fluid (CSF) markers for acute brain injury in the rat. Here, we investigate relationships between CSF changes in these novel markers and the severity of acute ischemic brain injury. Rats underwent sham surgery or 3,6,8, or 10 mins of transient global forebrain ischemia. At 48 h after insult, CSF levels of 14-3-3beta, 14-3-3zeta, and calpain cleavage products of alpha-spectrin and tau were quantified. Regional acute neurodegeneration was assessed by Fluoro-Jade and silver impregnation staining, and confirmed by immunohistochemical detection of the activation of calpain and caspase, cysteine proteases involved in neurodegenerative signaling. Ischemic neurodegeneration and activation of at least one cysteine protease were observed in the hippocampal CA1 sector, dentate hilus, caudate nucleus, parietal cortex, thalamus, and inferior colliculus. As expected, the total number of degenerating cells increased as a function of ischemia duration. Cerebrospinal fluid levels of the four marker proteins increased markedly after ischemia, and rose in proportion with its duration. Irrespective of the length of ischemia, CSF levels of the neuron-enriched proteins 14-3-3beta and calpain-cleaved tau correlated significantly with the magnitude of acute ischemic neurodegeneration. Additionally, CSF levels of the two proteins correlated with one another. These results show that certain proteins released from degenerating neurons are CSF markers for brain injury in the rat whose levels reflect the severity of acute ischemic neurodegeneration. Measurement of 14-3-3beta and calpain-cleaved tau may be useful for the minimally invasive diagnosis, prognosis, and therapeutic evaluation of acute brain damage.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0271-678X
pubmed:author
pubmed:issnType
Print
pubmed:volume
25
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1433-44
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
2005
pubmed:articleTitle
Novel surrogate markers for acute brain damage: cerebrospinal fluid levels corrrelate with severity of ischemic neurodegeneration in the rat.
pubmed:affiliation
Department of Pharmacology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104-6084, USA. siman@pharm.med.upenn.edu
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, N.I.H., Extramural