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AJNR - American Journal of Neuroradiology

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The Search for Neuroprotective Strategies in Stroke

Gary H. Danton^a and W. Dalton Dietrich^a,b

^a Department of Neurological Surgery, The Miami Project to Cure Paralysis, FL
^b Department of Neurology, University of Miami School of Medicine, FL

View larger version (33K): [in a new window]   FIG 1. Schematic of the ischemic cascade. The numbers 1–12 correspond to the numbers 1–12 at each class of therapy in Table 2. When the presynaptic neuron becomes ischemic, it depolarizes, opening sodium (Na) and potassium (K) channels (1, 2). This leads to opening of calcium (Ca) channels and influx of calcium (3). The presynaptic cell releases glutamate that activates NMDA, AMPA, and MGLURs (4–6), which permits calcium entry in the postsynaptic cell. NAALADase inhibitors limit the amount of glutamate available for release (7). GABA agonists inhibit depolarization and prevent calcium entry (8). During reperfusion, upregulated adhesion molecules attract inflammatory cells that contribute to vessel occlusion and cytotoxin production (9). MMPs degrade the basement membrane around vessels, enhancing inflammation and edema (10). Inflammatory cells, ischemic neurons, and glia produce free radicals that contribute to cell damage and death (11). HMG-CoA reductase inhibitors (statins) stabilize the endothelium through upregulation of endothelial nitric oxide synthase (NOS, 12).