Figure 1

Major cellular patho-physiological mechanisms of ischemic stroke. Ischemia-induced energy failure leads to the depolarization of neurons. Activation of specific glutamate receptors dramatically increases intracellular Ca²⁺, and Na⁺, and K⁺ is released into the extracellular space. Edema results from water shifts to the intracellular space. Increased levels of intracellular messenger Ca²⁺ activates proteases, lipases and endonucleases. Free radicals are generated which damage membranes, mitochondria and DNA, in turn triggering cell death and inducing the formation of inflammatory mediators, which then induce JNK, p-38, NFκB and AP-1 activation in glial cells, endothelial cells, and infiltrating leukocytes. This culminates in pro-inflammatory cytokine and chemokine secretion and leads to the invasion of leukocytes via up-regulation of endothelial adhesion molecules.