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

Stroke is the second largest cause of mortality and a significant cause of acquired disability associated with a substantial socioeconomic burden in the world. It has been estimated that almost more than six million people die each year from stroke. Acute ischemic stroke is the most frequent stroke subtype, accounting for more than 80% of all strokes. This condition is caused in most cases due to blockage of a supplying arterial vessel by an embolus or thrombus [1,2]. Ischemia triggers a complex series of events that can result in brain injury, in which inflammation and apoptosis are significant scenarios in the progression of brain damage after ischemia [3,4]. During ischemia, there is increased activation of transcriptional regulators such as nuclear factor-kappa B (NF-κB) [5]. NF-κB is known as a multi-protein complex which located in different cells types of the nervous system. This important protein exerts roles in various central nervous system diseases including ischemic stroke. NF-κB signaling pathway regulates the expression proinflammatory cytokines as Tumor necrosis factoralpha (TNF-α) [5,6]. TNF-α is an essential signaling protein in inflammatory reactions. It also can act as a central mediator in physiological processes of homeostasis and host defense. In ischemia, TNF-α is produced by neurons and microglia, which could stimulate apoptosis pathway via its receptor, TNF-α receptor 1 (TNFR1) [7-9]. Apoptosis is occurred by the activation of a class of cysteine proteases, termed caspases, and B-cell lymphoma 2 (Bcl-2) family proteins [10]. The proteins of this family, contained pro-apoptotic and anti-apoptotic proteins, play a crucial role in mitochondrial membrane integrity [11]. Ischemia induces outer mitochondrial membrane permeabilization. Hence, intermembrane space protein, cytochrome c, is translated into the C o r re s p o n d e n c e