Activation of Inflammatory Mediators and Apoptosis Biomarkers Following Endothelin-1 Induced Acute Ischemia in Rats

  • Fatemeh Farokhi-Sisakht Neurosciences Research Center, Tabriz University of Medical Sciences; Department of Neuroscience, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
  • Saeed Sadigh-Eteghad Neurosciences Research Center, Tabriz University of Medical Sciences
  • Pouran Karimi Neurosciences Research Center, Tabriz University of Medical Sciences


Objective: Specific animal models have been created to mimic ischemic stroke. Endothelin-1 (ET-1) is a vasoconstrictor peptide that is increasingly utilized as a preclinical method for inducing cerebral ischemia in rodents. In the present study, we investigated the changes of inflammatory and apoptosis biomarkers in the acute phase of ET-1- induced ischemia.

Materials and Methods: 15 male rats were randomly divided into 3 groups (n=5): Control, sham, and ischemia. Rats of sham and ischemic groups underwent stereotaxic intrahippocampal injection of saline and ET-1, respectively. The protein levels of Nuclear factor-kappa B (NF-κB), tumor necrosis factor-alpha (TNF-α), tumor necrosis factor-alpha receptor 1 (TNFR1), cytochrome c, B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X protein (Bax), and cleaved caspase-3 was evaluated by western blotting at 24 hours after surgery.

Results: Our finding were the first to show that ET-1 markedly upregulated the inflammatory and apoptotic proteins except for NF-κB in the acute stage of ischemia.

Conclusion: These data demonstrate that ischemia with ET-1 triggers inflammatory and apoptosis responses, which may be involved in exacerbating the ischemic injury.

Original Article