, 14:1308 | Cite as

Tumor necrosis factor-alpha participates in apoptosis in the limbic system after myocardial infarction

  • S. Kaloustian
  • T. M. Bah
  • I. Rondeau
  • S. Mathieu
  • L. Lada-Moldovan
  • P. Ryvlin
  • R. Godbout
  • G. Rousseau
Original Paper


This study was designed to determine the role of tumor necrosis factor-alpha (TNFα) in apoptosis observed in the myocardium and limbic system after myocardial ischemia. PEG sTNFRI, a recombinant, human, soluble p55 Type 1 TNF receptor (3 mg/kg) or vehicle (saline) was administered s.c. to male Sprague-Dawley rats on days 5, 3 and 1 before myocardial ischemia. The animals were then subjected, under anesthesia, to left anterior descending coronary artery occlusion for 40 min, followed by 15-min or 72-h reperfusion. Caspase-3 and -8 activities as well as terminal dUTP nick-end labelling-positive cells were examined in the myocardium (subendocardial and subepicardial regions), lateral (LA) and medial amygdala (MA) and hippocampus (CA1, CA3, dentate gyrus (DG)). After 15 min of reperfusion, the subendocardial and CA1 regions presented an increase in caspase-3 activity, whereas caspase-8 activity appeared to be augmented in the DG. PEG sTNFRI inhibited caspase-8 activation in the DG. After 72 h of reperfusion, plasma TNFα levels were reduced in the treated groups. The DG, CA1, CA3 and MA showed an increment of caspase-8 activity, which was reversed by PEG sTNFRI, except in the MA. Furthermore, caspase-3 activity was increased in the CA1, DG, LA and MA. These results indicate that TNFα contributes to apoptosis via activation of the extrinsic pathway in the limbic system after myocardial infarction, which is not the case in the myocardium.


Myocardial infarction Apoptosis Caspase-3 Caspase-8 Hippocampus Amygdala TNFα PEG sTNFRI 


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Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  • S. Kaloustian
    • 1
    • 3
    • 4
  • T. M. Bah
    • 3
  • I. Rondeau
    • 1
    • 3
  • S. Mathieu
    • 3
  • L. Lada-Moldovan
    • 1
    • 3
  • P. Ryvlin
    • 4
  • R. Godbout
    • 2
    • 3
  • G. Rousseau
    • 1
    • 3
  1. 1.Département de pharmacologieUniversité de MontréalQuébecCanada
  2. 2.Département de psychiatrieUniversité de MontréalQuébecCanada
  3. 3.Centre de biomédecineHôpital du Sacré-Coeur de MontréalMontréalCanada
  4. 4.Département de Neurologie Fonctionnelle et ÉpileptologieHospices Civils de Lyon et Université Claude Bernard Lyon 1LyonFrance

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