Aggravation of brain injury after transient focal ischemia in p53-deficient mice

Keiichiro Maeda, Ryuji Hata, Frank Gillardon, Konstantin Alexander Hossmann

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

The transcriptional factor p53 is a regulatory protein which contributes to the preservation of tissue integrity by promoting either DNA repair or apoptosis. To establish the pathophysiological role of this protein in ischemia, we produced 1 h transient middle cerebral artery (MCA) occlusion in normal and in p53-deficient mice and investigated the resulting tissue damage by multiparametric imaging. Possible genetic influences on the angioarchitecture of the MCA territory and blood flow were examined by intravascular latex infusion and laser-Doppler flowmetry. Wild-type (p53+/+), heterozygous (p53+/-) and homozygous (p53-/-) mice deficient for the p53 gene did not differ in respect to angioarchitecture or the effect of vascular occlusion on blood flow and general physiological parameters. Twenty-four hours after 1 h MCA occlusion, mice revealed a gene dose-dependent decline in the size of metabolic disturbances (ATP depletion and inhibition of protein synthesis) and histological injury (Cresyl Violet staining). DNA fragmentations detected by terminal deoxynucleotidyl transferase-mediated UTP nick end labeling (TUNEL) did not differ in the three groups and were only present in ATP-depleted tissue. Our findings suggest that after transient focal brain ischemia p53 prevents rather than aggravates brain injury, and that this effect is brought about by mechanisms that are unrelated to the pro-apoptotic properties of this gene.

Original languageEnglish
Pages (from-to)54-61
Number of pages8
JournalMolecular Brain Research
Volume88
Issue number1-2
DOIs
Publication statusPublished - 31-03-2001
Externally publishedYes

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Brain Injuries
Ischemia
Middle Cerebral Artery Infarction
Adenosine Triphosphate
Tissue Preservation
Laser-Doppler Flowmetry
Uridine Triphosphate
Proteins
DNA Nucleotidylexotransferase
p53 Genes
Latex
Middle Cerebral Artery
DNA Fragmentation
Brain Ischemia
DNA Repair
Genes
Blood Vessels
Apoptosis
Staining and Labeling
Wounds and Injuries

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cellular and Molecular Neuroscience

Cite this

Maeda, Keiichiro ; Hata, Ryuji ; Gillardon, Frank ; Hossmann, Konstantin Alexander. / Aggravation of brain injury after transient focal ischemia in p53-deficient mice. In: Molecular Brain Research. 2001 ; Vol. 88, No. 1-2. pp. 54-61.
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Aggravation of brain injury after transient focal ischemia in p53-deficient mice. / Maeda, Keiichiro; Hata, Ryuji; Gillardon, Frank; Hossmann, Konstantin Alexander.

In: Molecular Brain Research, Vol. 88, No. 1-2, 31.03.2001, p. 54-61.

Research output: Contribution to journalArticle

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