Abstract

INFLAMMATION AND ANTI-INFLAMMATORY STRATEGIES IN STROKE

Manzoor A Mir and Raid S Albaradie

Abstract

Stroke is an important public health issue due to high rates ofdisability, morbidity/ mortality and is now the third leading cause ofdeath after heart disease and cancer affecting 15 million peopleworldwide each year. In spite of extensive research in the field ofstroke during past decade the current therapeutic strategies have beenlargely unsuccessful. One possible explanation is that research andpharmacological management have focused on very early events inbrain ischemia. Two important pathophysiological mechanismsinvolved during ischemic stroke are oxidative stress and inflammation.Brain tissue is not well equipped with antioxidant defenses, so reactiveoxygen species and other free radicals/oxidants, released by inflammatory cells, threatentissue viability in the vicinity of the ischemic core. Recent studies have shown that brainischemia and trauma elicit strong inflammatory reactions driven by both external and braincells. Clinical observations suggest that patients with stroke have higher plasma levels ofinflammatory cytokines or soluble adhesion molecules and anti-inflammatory therapy iseffective at reducing stroke incidence in not only animal models, but in humans as well. Thissuggests that inflammation might directly affect the onset of stroke. The recognition ofinflammation as a fundamental response to brain ischemia provides novel opportunities fornew anti-inflammatory therapies. Currently, little is known about endogenous counterregulatory immune mechanisms. Statins have been shown to decrease the stroke incidencevia anti-inflammatory effects that are both dependent and independent of their cholesterolloweringeffects. Here in this review we will discuss the molecular aspects of oxidative stressand inflammation in ischemic stroke. We will also present the latest findings about thecellular 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.

Keywords: Neuroinflammation, antioxidant, macrophages, Ischemia, cytokines, ischemic, statins, brain, immune reactions.