A schematics view of ischemic stroke mechanisms. Activation of glutamate receptors following ischemic stroke leads to excitotoxicity and calcium influx. This impairs the neuronal homeostasis leading to activation of several calcium dependent pathways that include proteases and nucleases. Reperfusion aggravates the neuronal damage by forming free radicals that damage the membranes, proteins and DNA. Further, the opening of mitochondrial permeability transition pore releases various proapoptotic molecules including cytochrome C that activate apoptotic cell death. Neuronal death following ischemia will be a result of necrotic, apoptotic and necroptotic mechanisms depending on the severity of insult.

A schematic view of various targeted neuroprotective approaches for minimizing post-stroke brain damage. Stroke activates various pathophysiological mechanisms including glutamate excitotoxicity, oxidative stress, and inflammation that impair neuronal survival and results in neuronal death through necrosis, apoptosis or necroptosis. Moreover, stroke also impairs neuromodulation and regeneration of cells. Therefore, strategies that can target these pathways as well as restore growth factors and initiate regeneration of neurons may provide beneficial outcome following stroke. Adapted and modified from Mehta et al. (2009).