Inhibition of interleukin-1β converting enzyme family proteases (caspases) reduces cold injury-induced brain trauma and DNA fragmentation in mice

Yuiko Morita-Fujimura, Miki Fujimura, Makoto Kawase, Kensuke Murakami, Gyung Whan Kim, Pak H. Chan

Research output: Contribution to journalArticle

42 Citations (Scopus)

Abstract

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 mm3, z-VAD.FMK-treated animals; 7.46±3.53 mm3, 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.

Original languageEnglish
Pages (from-to)634-642
Number of pages9
JournalJournal of Cerebral Blood Flow and Metabolism
Volume19
Issue number6
DOIs
Publication statusPublished - 1999 Jan 1

Keywords

  • Caspase inhibitor
  • Cold injury
  • Neuronal apoptosis
  • Vasogenic edema

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology
  • Cardiology and Cardiovascular Medicine

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