Tumor necrosis factor-α mediates hemolysis-induced vasoconstriction and the cerebral vasospasm evoked by subarachnoid hemorrhage

Carmine Vecchione, Alessandro Frati, Alba Di Pardo, Giuseppe Cifelli, Daniela Carnevale, Maria Teresa Gentile, Rosa Carangi, Alessandro Landolfi, Pierluigi Carullo, Umberto Bettarini, Giovanna Antenucci, Giada Mascio, Carla Letizia Busceti, Antonella Notte, Angelo Maffei, Gian Paolo Cantore, Giuseppe Lembo

Research output: Contribution to journalArticlepeer-review


Hypertension can lead to subarachnoid hemorrhage and eventually to cerebral vasospasm. It has been suggested that the latter could be the result of oxidative stress and an inflammatory response evoked by subarachnoid hemorrhage. Because an unavoidable consequence of hemorrhage is lysis of red blood cells, we first tested the hypothesis on carotid arteries that the proinflammatory cytokine tumor necrosis factor-α contributes to vascular oxidative stress evoked by hemolysis. We observed that hemolysis induces a significant increase in tumor necrosis factor-α both in blood and in vascular tissues, where it provokes Rac-1/NADPH oxidase-mediated oxidative stress and vasoconstriction. Furthermore, we extended our observations to cerebral vessels, demonstrating that tumor necrosis factor-α triggered this mechanism on the basilar artery. Finally, in an in vivo model of subarachnoid hemorrhage obtained by the administration of hemolyzed blood in the cisterna magna, we demonstrated, by high-resolution ultrasound analysis, that tumor necrosis factor-α inhibition prevented and resolved acute cerebral vasoconstriction. Moreover, tumor necrosis factor-α inhibition rescued the hemolysis-induced brain injury, evaluated with the method of 2,3,5-triphenyltetrazolium chloride and by the histological analysis of pyknotic nuclei. In conclusion, our results demonstrate that tumor necrosis factor-α plays a crucial role in the onset of hemolysis-induced vascular injury and can be used as a novel target of the therapeutic strategy against cerebral vasospasm.

Original languageEnglish
Pages (from-to)150-156
Number of pages7
Issue number1
Publication statusPublished - Jul 1 2009


  • Cerebrovascular disease
  • Cytokines
  • Inflammation
  • Oxidant stress
  • Subarachnoid hemorrhage

ASJC Scopus subject areas

  • Internal Medicine


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