Role of Inflammation in Stroke: Benefits or Harm?

Abstract

At the onset of the 21^st century, stroke is the third leading cause of death in most developed countries and the primary cardiovascular cause of death in Japan and China. The health burden of the disease is staggering as loss of productive life inflicts heavy toll on the patients, families and society. Yet, this disease has no effective therapeutic beyond a limited (<5%) treatment with thrombolytics that carry significant adverse effect. This situation is prominent in spite of intense research efforts and numerous clinical trials attempting to develop drugs that reduce morbidity and mortality from stroke. So far, the focus of drug development efforts targeted modulators of ion channels (Ca⁺², Na⁺), scavengers of oxygen radicals and antagonists of excitotoxic neurotransmitters (primarily glutamate and glycine receptors). However, all clinical trials have failed so far due to lack of efficacy, adverse effects or other development difficulties. Debates on the reasons for the possible causes of failure include wrong animal models, wrong mechanism of action, poor clinical design, inadequate timing of treatment etc. While this debate is ongoing, the stroke research community seems to have been disenchanted from the ‘classical’ targets for drug development (vide supra) as evidence by emerging hope that other avenues such as ‘reconstruction’, ‘apoptosis’ and ‘inflammation’ are better pastures for future successes.