Tumor necrosis factor-alpha increases cerebral blood flow and ultrastructural capillary damage through the release of nitric oxide in the rat brain

Eszter Farkas, Zoltán Süle, Valéria Tóth-Szuki, Adrienne Mátyás, Péter Antal, Ibolya G. Farkas, András Mihály, Ferenc Bari

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Tumor necrosis factor-α (TNFα) is a proinflammatory cytokine implicated in cerebrovascular pathology. The aim of the present study was to characterize the simultaneous effects of an intracarotid administration of TNFα on cerebral blood flow (CBF) and the ultrastructure of the blood-brain barrier (BBB) and to determine whether nitric oxide (NO) is a mediator of the TNFα-induced alterations in CBF and BBB. TNFα (2.5 μg/kg) or saline was infused into the right common carotid artery of male Wistar rats (n = 70). NO production was inhibited with l-NAME (20 mg/kg, i.v.). CBF was monitored for 2 h with laser-Doppler flowmetry. Tissue samples were taken from the unilateral frontoparietal cortex and prepared for electron microscopy. The proportion of capillaries with swollen astrocytic endfeet and the lumen diameter of the capillaries were measured. TNFα significantly increased CBF, which reached a maximum of 190% of the baseline 1 h after the cessation of TNFα infusion. l-NAME completely prevented the increase in CBF. TNFα elevated the swelling of the astrocytic endfeet from a baseline value of 22.4 ± 9.35% to 64.9 ± 3.16%. The administration of l-NAME before TNFα infusion prevented the astrocytic swelling. These results demonstrate that TNFα increases CBF and the swelling of astrocytes through the production of NO. Our data additionally demonstrate that the breakdown of the BBB by circulating TNFα may involve the astrocytic endfeet.

Original languageEnglish
Pages (from-to)113-119
Number of pages7
JournalMicrovascular Research
Volume72
Issue number3
DOIs
Publication statusPublished - Nov 1 2006

Keywords

  • Astrocyte
  • Blood-brain barrier
  • Cerebral blood flow
  • Nitric oxide
  • TNFα

ASJC Scopus subject areas

  • Biochemistry
  • Cardiology and Cardiovascular Medicine
  • Cell Biology

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