Angiotensin-(1-7) protects from central nervous system damage induced by Shiga toxin 2-producing enterohemorrhagic Escheria Coli

GIRONACCI MM, HÖCHT C, TAIRA C, GOLDSTEIN J

Boston

Congreso; 33. 9th Triennial International Symposium on Shiga Toxin (Verocytotoxin)-producing Escherichia coli (VTEC) Meeting; 2015

Several evidences showed a cerebroprotective action for angiotensin (Ang) (1-7) but neither of them demonstrated its cellular target for this protective effect. Our aim was to investigate the cellular type protected by Ang-(1-7) by transmission electron microscopy in the model of brain damage induced by Shiga toxin 2 (Stx2)-producing enterohemorrhagic Escherichia Coli. Adult male Wistar rats were injected with saline solution or Stx2 or Stx2 plus Ang-(1-7) or Stx2 plus Ang-(1-7) plus A779 into the anterior hypothalamic area (AHA). Rats received a single injection of Stx2 at the beginning while Ang-(1-7), A779 or saline was given daily as a single injection during 8 days. Ultrastructural changes were analyzed by transmission electron microscopy. Stx2 induced neurodegeneration, axon demyelination, alterations in synapse and oligodendrocyte and astrocyte damage, accompanied with edema. Ang-(1-7) partially prevented neuronal damage: 55.6+9.5 % of the neurons were protected from the damage triggered by the toxin. In addition, Ang-(1-7) hampered the Stx2-induced demyelination in 92+4% of the axons. Oligodendrocyte damage caused by Stx2 was prevented by Ang-(1-7) but atrocytes were partially protected by the peptide (38+5 % of astrocytes were preserved). The Stx2-induced synapse dysfunction was reverted by Ang-(1-7). The number of activated microglial cells induced by Stx2 was reduced by 50% by Ang-(1-7) treatment (P