Linked Life Data

10938439

Source:http://linkedlifedata.com/resource/pubmed/id/10938439

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2000-10-19
pubmed:abstractText
Evidence indicates that both necrotic and apoptotic cell death contribute to tissue injury and neurological dysfunction following spinal cord injury. Caspases have been implicated as important mediators of apoptosis following acute central nervous system insults. We investigated whether caspase-1 and caspase-3 are involved in spinal cord injury-mediated cell death, and whether caspase inhibition may reduce tissue damage and improve outcome following spinal cord injury. We demonstrate a 17-fold increase in caspase-1 activity in traumatized spinal cord samples when compared with samples from sham-operated mice. Caspase-1 and caspase-3 activation were also detected by western blot following spinal cord injury, which was significantly inhibited by the broad caspase inhibitor N-benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone. By immunofluorescence or in situ fluorogenic substrate assay, caspase-1 and caspase-3 expression were detected in neuronal and non-neuronal cells following spinal cord injury. N-Benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone treated mice, and transgenic mice expressing a caspase-1 dominant negative mutant, demonstrated a significant improvement of motor function and a reduction of lesion size compared with vehicle-treated mice. Our results demonstrate for the first time that both caspase-1 and caspase-3 are activated in neurons following spinal cord injury, and that caspase inhibition reduces post-traumatic lesion size and improves motor performance. Caspase inhibitors may be one of the agents to be used for the treatment of spinal cord injury.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
0306-4522
pubmed:author
pubmed:issnType
Print
pubmed:volume
99
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
333-42
pubmed:dateRevised
2009-11-3
pubmed:meshHeading
pubmed:year
2000
pubmed:articleTitle
Functional role and therapeutic implications of neuronal caspase-1 and -3 in a mouse model of traumatic spinal cord injury.
pubmed:affiliation
Neuroapoptosis Laboratory and Neurosurgical Service, Department of Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.