Mechanisms of Stroke Induced Neuronal Death: Multiple Therapeutic Opportunities

Abstract

| Stroke is one of the major contributors of mortality and morbidity worldwide. It results due to sudden blockade of blood flow into the brain thereby leading to breakdown of hemodynam-ic, biochemical and metabolic processes in the affected territory. These alterations are dependent on the severity and duration of the ischemia and modulated by pathophysiologic mechanisms that in-clude excitotoxicity, calcium overload, oxidative stress, endoplasmic reticulum stress, mitochondrial dysfunction, acidosis, inflammation and activation of cell death pathways. As there is no current therapy to minimize post-stroke brain damage and most of the clinical trials failed, it is impera-tive to design novel approaches including glutamate receptor antagonists, free radical scavengers/ anti-oxidants, anti-inflammatory and anti-apoptotic agents, and growth factors to prevent the pro-gression and increase the plasticity of neuronal damage after stroke. Additionally, rigorous in vitro and in vivo animal testing of potential drugs molecules is necessary to reduce the failure of clinical trials.