The NF-κB inhibitor diethyldithiocarbamate (DDTC) increases brain cell death in a transient middle cerebral artery occlusion model of ischemia

William D Hill, David C Hess, James Edwin Carroll, Chandramohan G. Wakade, Eugene F. Howard, Qiang Chen, Charles Cheng, Angeline Martin-Studdard, Jennifer L Waller, Richard A. Beswick

Research output: Contribution to journalArticle

55 Citations (Scopus)

Abstract

A transient ischemic middle cerebral artery occlusion model of stroke was used to examine the role of the transcription factor NF-κB in cell death as measured by DNA fragmentation and infarction volume. The left middle cerebral artery was occluded for either 30 min or 2 h in rats. One set of animals was pretreated with diethyldithiocarbamate (DDTC), an inhibitor of NF-κB, 30 min prior to reperfusion. The animals were reperfused and allowed to survive for 2 or 7 days. DNA fragmentation was assayed by in situ end labeling in the stroke core and penumbral regions. Specific cortical and subcortical regions were measured using quantitative image analysis. DNA fragmentation was seen only on the ischemic side of the brains in all cases. Overall, the DDTC-treated groups showed significantly increased DNA fragmentation within the ischemic side compared to the saline control groups. DDTC treatment also caused an increase in stroke volume based on triphenyl tetrazolium chloride staining. Electrophoretic mobility shift assays showed NF-κB activation peaking 15 min following reperfusion and that this activation was blocked by the DDTC treatment. This study suggests that the use of NF-κB inhibitors to block cell death following stroke needs to be carefully examined because global inhibitors may not promote neuronal survival.

Original languageEnglish (US)
Pages (from-to)375-386
Number of pages12
JournalBrain Research Bulletin
Volume55
Issue number3
DOIs
StatePublished - Aug 20 2001

Fingerprint

Ditiocarb
Brain Death
Middle Cerebral Artery Infarction
DNA Fragmentation
Cell Death
Ischemia
Stroke
Reperfusion
Middle Cerebral Artery
Electrophoretic Mobility Shift Assay
Stroke Volume
Infarction
Chlorides
Transcription Factors
Staining and Labeling
Control Groups
Brain

Keywords

  • Apoptosis
  • Cerebral infarction
  • Delayed cell death
  • Nuclear factor-κB
  • Stroke

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

The NF-κB inhibitor diethyldithiocarbamate (DDTC) increases brain cell death in a transient middle cerebral artery occlusion model of ischemia. / Hill, William D; Hess, David C; Carroll, James Edwin; Wakade, Chandramohan G.; Howard, Eugene F.; Chen, Qiang; Cheng, Charles; Martin-Studdard, Angeline; Waller, Jennifer L; Beswick, Richard A.

In: Brain Research Bulletin, Vol. 55, No. 3, 20.08.2001, p. 375-386.

Research output: Contribution to journalArticle

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