Page - (000181) - in Biomedical Chemistry: Current Trends and Developments

Dong, 2009). Stroke is a complex and devastating disease, constituting the second leading cause of death worldwide and the leading cause of acquired disability in adults (Brouns, 2009; Lloyd-Jones, 2009; Moskowitz, 2010). Stroke can be subdivided into ischemic and hemorrhagic (Doyle, 2008). Ischemic strokes are more frequent and are caused by a thrombosis or an embolic occlusion of a cerebral blood vessel, more frequently the middle and anterior cerebral arteries, or a general hypo-perfusion, all of which result in a constraint of blood flow to the brain, reducing the delivery of substrates, particularly oxygen and glucose, and ATP production (Dirnagl, 1999; Doyle, 2008; Lloyd-Jones, 2009). Because of its high metabolic activity, together with large concentrations of glutamate (Choi, 1992), the brain is particularly vulnerable to ischemic insults. The ischemic core is the irreversibly damaged tissue characterized by less than 20% of normal blood flow levels, reduced ATP levels and irreversible energetic failure (Lo, 2008b). Cells in the core are killed rapidly by proteolysis, lypolysis, bioenergetic failure and collapse of ion homeostasis (Doyle, 2008; Brouns, 2009). In the peripheral areas of stroke, between the normal brain and the damaged core, lies the ischemic penumbra or peri-infarct zone (Astrup, 1981). In this region, blood flow deficits are less severe, hardly sufficient to support basal ATP levels and normal ionic gradients (Moskowitz, 2010). Therefore, in the penumbra region the tissue is functionally impaired but potentially salvageable, and can be rescued by enhancing blood flow or interfering with the ischemic cascade (Lo, 2008b; 2008a; Brouns, 2009). With time, the infarct core expands into the ischemic penumbra, so, accurate detection of this tissue at risk can help to identify patients who might benefit from treatment with recombinant tissue plasminogen activator (rtPA), the only approved drug to treat acute stroke patients, by promoting clot lysis and reperfusion, therefore restore blood flow at an early time point (NINDS, 1995; Paciaroni, 2009). The decreased ATP production leads to the dysfunction of energy-dependent ion transport pumps, and to the consequent depolarization of neurons and glia (Katsura, 1994; Martin, 1994). The Na+/K+ ATPase at the plasma membrane of neurons maintains high K+ and low Na+ intracellular concentrations, that are essential for the propagation of action