Pharmacology of neuroprotection in acute ischemic stroke

Introduction. Stroke leads the list of causes of disability in adults and represents the second leading cause of death worldwide. Knowledge about the pathophysiology of ischemic stroke has improved substantially over the past 25 years, and, as a result of this, new therapeutic strategies have been developed with two main aims: restoration of cerebral flow and the minimization of the deleterious effects of ischemia on neurons. Although so far there are no drugs approved for the neuroprotection therapy in stroke, there are some compounds with promising results. Development. This paper makes a critical review of several studies on the preclinical stroke neuroprotection with drugs aimed to protect the brain tissue adjacent to the damaged central area or ischemic penumbra zone until either the physiological mechanisms or the treatment stop the ischemic insult. We expose the potential neuroprotective properties of these treatments mainly based on inhibiting excitotoxicity processes mediated by gamma-aminobutyric acid receptors, glutamate release and interacting with ion channels such as calcium and sodium. We focus on drugs which have shown to be capable of modulating intracellular degenerative pathways in mitochondria mediated apoptosis or the expression of apoptosis or the expression of apoptotic proteins in experimental models. Conclusion. It is very likely that the neuroprotective effects require a poly-drug therapy that combines different mechanisms of action.