Inflammatory Mechanisms as Potential Therapeutic Targets in Stroke

Abstract

Stroke is an important public health issue due to high rates of disability, morbidity/mortality and is now the third leading cause of death after heart disease and cancer affecting 15 million people worldwide each year. In spite of extensive research in the field of stroke during past decade the current therapeutic strategies have been largely unsuccessful. One possible explanation is that research and pharmacological management have focused on very early events in brain ischemia. Two important pathophysiological mechanisms involved during ischemic stroke are oxidative stress and inflammation. Brain tissue is not well equipped with antioxidant defenses, so reactive oxygen species and other free radicals/oxidants, released by inflammatory cells, threaten tissue viability in the vicinity of the ischemic core. Recent studies have shown that brain ischemia and trauma elicit strong inflammatory reactions driven by both external and brain cells. Clinical observations suggest that patients with stroke have higher plasma levels of inflammatory cytokines or soluble adhesion molecules and anti-inflammatory therapy is effective at reducing stroke incidence in not only animal models, but in humans as well. This suggests that inflammation might directly affect the onset of stroke. The recognition of inflammation as a fundamental response to brain ischemia provides novel opportunities for new anti-inflammatory therapies. Currently, little is known about endogenous counter regulatory immune mechanisms. Statins have been shown to decrease the stroke incidence via anti-inflammatory effects that are both dependent and independent of their cholesterol-lowering effects. Here in this review we will discuss the molecular aspects of oxidative stress and inflammation in ischemic stroke. We will also present the latest findings about the cellular and humoral aspects of immune and inflammatory reactions in the brain. This will increase our understanding regarding neuro-injuries and role immune reactions play in the brain milieu. This all may have an impact on the potential therapeutic strategies that target neuro-inflammation and the innate immune system.