In:
Journal of Cerebral Blood Flow & Metabolism, SAGE Publications, Vol. 19, No. 6 ( 1999-06), p. 634-642
Kurzfassung:
The authors examined the effect of z-VAD.FMK, an inhibitor that blocks caspase family proteases, on cold injury-induced brain trauma, in which apoptosis as well as necrosis is assumed to play a role. A vehicle alone or with z-VAD.FMK was administered into the cerebral ventricles of mice 15 minutes before and 24 and 48 hours after cold injury. At 24 hours after cold injury, infarction volumes in the z-VAD.FMK-treated animals were significantly smaller than infarction volumes in the vehicle-treated animals, and were further decreased at 72 hours (0.92 ± 1.80 mm 3 , z-VAD.FMK-treated animals; 7.46 ± 3.53 mm 3 , vehicle-treated animals; mean ± SD, n = 7 to 8). The amount of DNA fragmentation was significantly decreased in the z-VAD.FMK-treated animals compared with the vehicle-treated animals, as shown by terminal deoxynucleotidyl transferase-mediated uridine 5'-triphosphate-biotin nick end labeling staining and DNA gel electrophoresis. By Western blot analysis, both the proform and activated form of interleukin-1β converting enzyme (caspase 1) were detected in the control brain, and the activated form showed moderate reduction after cold injury-induced brain trauma. These results indicate that caspase inhibitors could reduce cold injury-induced brain trauma by preventing neuronal cell death by DNA damage. The caspase family proteases appear to contribute to the mechanisms of cell death in cold injury-induced brain trauma and to provide therapeutic targets for traumatic brain injury.
Materialart:
Online-Ressource
ISSN:
0271-678X
,
1559-7016
DOI:
10.1097/00004647-199906000-00006
Sprache:
Englisch
Verlag:
SAGE Publications
Publikationsdatum:
1999
ZDB Id:
2039456-1
Permalink
