Angiotensin-(1-7) protects from brain damage induced by shiga toxin 2-producing enterohemorrhagic Escherichia coli

作者：Goldstein Jorge; Carden Tomas R; Perez Maria J; Taira Carlos A; Hocht Christian; Gironacci Mariela M

来源：American Journal of Physiology - Regulatory, Integrative and Comparative Physiology, 2016, 311(6): R1173-R1185.

DOI：10.1152/ajpregu.00467.2015

• angiotensin-(1-7)
• Mas receptor
• neuron
• oligodendrocyte
• astrocyte

Shiga toxin 2 (Stx2)-producing enterohemorrhagic induced brain damage. Since a cerebroprotective action was reported for angiotensin (Ang)-(1-7), our aim was to investigate whether Ang-(1-7) protects from brain damage induced by Stx2-producing enterohemorrhagic Escherichia coli. The anterior hypothalamic area of adult male Wistar rats was injected with saline solution or Stx2 or Stx2 plus Ang-(1-7) or Stx2 plus Ang-(1-7) plus A779. Rats received a single injection of Stx2 at the beginning of the experiment, and Ang-(1-7), A779, or saline was administered daily in a single injection for 8 days. Cellular ultrastructural changes were analyzed by transmission electron microscopy. Stx2 induced neurodegeneration, axonal demyelination, alterations in synapse, and oligodendrocyte and astrocyte damage, accompanied by edema. Ang-(1-7) prevented neuronal damage triggered by the toxin in 55.6 +/- 9.5% of the neurons and the Stx2-induced synapse dysfunction was reversed. In addition, Ang-(1-7) blocked Stx2-induced demyelination in 92 +/- 4% of the axons. Oligodendrocyte damage caused by Stx2 was prevented by Ang-(1-7) but astrocytes were only partially protected by the peptide (38 +/- 5% of astrocytes were preserved). Ang-(1-7) treatment resulted in 50% reduction in the number of activated microglial cells induced by Stx2, suggesting an anti-inflammatory action. All these beneficial effects elicited by Ang-(1-7) were blocked by the Mas receptor antagonist and thus it was concluded that Ang-(1-7) protects mainly neurons and oligodendrocytes, and partially astrocytes, in the central nervous system through Mas receptor stimulation.

• 出版日期2016-12