Linked Life Data

12625816

Source:http://linkedlifedata.com/resource/pubmed/id/12625816

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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2003-3-10
pubmed:abstractText
We investigated the potential neuroprotective effect of transient hypertension on neuronal cell death induced by ischemia-reperfusion. Recovery of neurons, terminally differentiated cells, is almost entirely dependent upon active transcription and repair of DNA damage. We focused on the histochemical detection of distribution of NOR (argyrophylic nucleolar proteins) reflecting nucleolar integrity, immunohistochemical detection of PARP-1 (poly(ADP-ribose) polymerase-1), MADD (mitogen-activated death domain), a protein accumulated in nucleoli upon stimulation by ischemia, the active form of caspase-3, a universal proteolytic enzyme of apoptosis. The terminal deoxynucleotidyl-transferase (TdT)-mediated dUTP-biotin nick-end-labeling method (TUNEL) proved the presence of in situ DNA fragmentation. We used the model of transient focal cerebral ischemia in rats with occlusion of middle cerebral artery. In experimental group of rats, the transient hypertension was induced by constriction of the abdominal aorta. The period of ischemia lasted 15, 30, 60 and 120 min followed by 48 h of reperfusion. We examined the frontal lobe of the ipsilateral hemisphere for apoptosis of neurons and compared it with the intact brain tissue. In normotensive rats with transient focal cerebral ischemia, we found disintegrated nucleoli of cortical as well as subcortical neurons at all investigated periods of ischemia, whereas the neurons of intact animals showed compact nucleoli with a few satellites. Nuclear positivity for MADD and PARP-1 was apparent in the neocortex after 15 min and peaked after 30 min of ischemia. On the other hand, the subcortical neurons showed nuclear positivity after 60 and 120 min. The immunohistochemical reaction for active caspase 3 was apparent after 30 min onwards predominantly in the cortex. The TUNEL staining was distinct after 60 and 120 min. In hypertensive rats, we found nucleolar disintegration, positivity for MADD, PARP-1 and caspase 3 after 30 min cortically and subcortically, followed by TUNEL positive staining of cortical neurons after 60 and 120 min. In summary, we detected delayed activation of neuronal apoptosis in transiently hypertensive rats with focal cerebral ischemia compared to normotensive animals. The apoptotic phenotype was confirmed by a panel of complementary methods showing rapid proteolysis-nucleolar segregation, MADD, PARP-1 and caspase-3 positivity as well as ultimate DNA fragmentation proved by the TUNEL assay.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
0862-8408
pubmed:author
pubmed:issnType
Print
pubmed:volume
52
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
117-22
pubmed:dateRevised
2008-4-2
pubmed:meshHeading
pubmed-meshheading:12625816-Animals, pubmed-meshheading:12625816-Apoptosis, pubmed-meshheading:12625816-Caspase 3, pubmed-meshheading:12625816-Caspases, pubmed-meshheading:12625816-Cerebral Cortex, pubmed-meshheading:12625816-Death Domain Receptor Signaling Adaptor Proteins, pubmed-meshheading:12625816-Guanine Nucleotide Exchange Factors, pubmed-meshheading:12625816-Hypertension, pubmed-meshheading:12625816-In Situ Nick-End Labeling, pubmed-meshheading:12625816-Infarction, Middle Cerebral Artery, pubmed-meshheading:12625816-Male, pubmed-meshheading:12625816-Neostriatum, pubmed-meshheading:12625816-Neurons, pubmed-meshheading:12625816-Nuclear Proteins, pubmed-meshheading:12625816-Poly(ADP-ribose) Polymerases, pubmed-meshheading:12625816-Rats, pubmed-meshheading:12625816-Rats, Wistar, pubmed-meshheading:12625816-Recovery of Function, pubmed-meshheading:12625816-Reperfusion Injury
pubmed:year
2003
pubmed:articleTitle
The onset of apoptosis of neurons induced by ischemia-reperfusion injury is delayed by transient period of hypertension in rats.
pubmed:affiliation
Institute of Pathophysiology, Medical School, Masaryk University, Brno, Czech Republic.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't