Cerebral ischemic injury causes a series of

Cerebral ischemic injury causes a series of cascade reactions, and the inflammatory response is one of the important mechanisms of ischemia reperfusion injury (Ahmad et al., 2014). At the early stage of ischemia, a large number of inflammatory cells are activated, releasing of cytokines, chemotactic factor and matrix metalloproteinase inflammatory mediators, thereby promoting neutrophil cells migrate to the GSK126 cost ischemic area, ultimately increasing the death of neurons and the whole brain injury (Tao et al., 2016; Amantea et al., 2015). Cerebral ischemia reperfusion by triggering TNF-a, IL-1, two key cytokine releases, triggering a series of leukocyte infiltration and inflammatory cytokine expression of inflammatory reaction activation is caused by an important pathological mechanism of brain injury (Chen et al., 2016; Liu et al., 2016; Khaliq et al., 2016; Zwagerman et al., 2010). NO has the function of neurotransmitter or neuromodulator. The excessive production of NO after cerebral ischemia reperfusion can activate guanine nucleotide cyclase, which further result in DNA damage and mediated neurotoxicity.
ICAM-1 in cerebral ischemia reperfusion injury through the white blood cells and endothelial cell adhesion leads to vascular blockage, and no reflow phenomenon occurred, aggravated ischemic brain damage (Zhao and Ashraf, 2016; Xie et al., 2016; Sun et al., 2012). S100-beta protein is considered to be a marker of glial cells, which can promote neuronal differentiation, axon growth, glial proliferation and the stability of intracellular calcium (Feng et al., 2016; Kaca-Orynska et al., 2010). When ischemia and hypoxia and other factors cause the blood brain barrier damage, S100-beta can damage the blood brain barrier to enter the blood circulation. Therefore, the serum levels of S100-protein can be a reference to determine the degree of brain damage and prognosis.

As the experimental results suggest, compared with the model mice, Rabdosia rubescens total flavonoids can significantly relieve the injury of brain in hippocampus and cortex nerve cells; experimental rat focal cerebral ischemia was to improve again perfusion model of nerve function defect score mortality; significantly reduce brain homogenate NOS activity and no content, MDA, IL-1, TNF-a, ICAM-1 content; increase in brain homogenate SOD and ATPase activity (P<0.05, P<0.01); reduce the serum S-100β protein content. Total flavonoids of the herb can inhibit the inflammatory response after ischemia, and improve the inflammatory response of a series of cascade reaction media and cytokines, which play a protective role in cerebral ischemia reperfusion injury. This study gives a better basis of pharmacological effects of Rabdosia rubescens treatment Bureau focal cerebral ischemia resistant disease, and offers the guidance for the deep research of clinical heat clearing, detoxifying, promoting blood circulation and removing blood stasis drugs for treatment of cerebral ischemia reperfusion injury, meanwhile providing experimental basis for the development of future rabdosia herb and product.
The authors acknowledge Fund project: Excellent science and technology innovation team in Henan Province (Grant No. TCJ2014-391); Natural Science Foundation of Henan Province (Grant No. 132300410019); Zhengzhou science and technology innovation team (131PCXTD612).

Inefficient vascular supply and the resultant reduction in tissue oxygen tension often lead to neovascularization in order to satisfy the needs of the tissue. The reliance of many cells on aerobic respiration as a mandatory energy source requires a variety of responses to oxygen lack or “hypoxia” (Darby and Hewitson, 2016). Both hypoxia (lack of oxygen relative to metabolic needs) and reoxygenation (reintroduction of oxygen to hypoxic tissue) are important in human pathophysiology because they occur in a wide variety of important clinical conditions. Prominent examples of tissue hypoxia that predispose to injury during reoxygenation include circulatory shock, myocardial ischemia, stroke, and transplantation of organs (Martindale and Holbrook, 2002; Wenger, 2002; Brady et al., 2006). At the cellular level, hypoxia activates numerous major signaling pathways, resulting in changes in gene expression, which influence the cellular ability to survive or die. Severe hypoxia, occurring at partial pressure of oxygen below 20mmHg, impairs cellular energy production and ion homeostasis, leading to cell injury and cell death. A lower degree of hypoxia, defined as between 50 and 100mmHg, may activate mechanisms that could produce cellular phenotype GSK126 cost more resistant to acute severe oxidative stress (Zweier and Talukder, 2006). This phenomenon is one of the most important components of different forms of ischemic heart diseases which include myocardial infarction also. Cellular models of hypoxia-reoxygenation (HR) have provided useful tools for the study of reactive species mediated mechanisms of cellular dysfunction in ischemia-reperfusion injury (Watkins et al., 1995). H9c2 cells are derived from embryonic rat heart and are generally accepted to be a good model for cardiomyoblast cells. These cells have been successfully implemented to study mechanisms of cellular and cardiac protection (Ekhterae et al., 1999; Ranki et al., 2002).