Abstract:

The central nervous system has a very high energy requirement. Accordingly,despite representing only 2% of the body’s mass, the brain uses 20% of the total oxygen consumption. Importantly, because most of this energy is used to maintain synaptic activity, even a mild decrease in its supply to the brain has deleterious implications for synaptic function.For example, only one minute of interruption of the cerebral blood flow during an acute ischemic stroke (AIS) is enough to destroy approximately 14 billion synapses (Saver, 2006). Importantly, because synaptic dysfunction leads to functional impairment, cerebral ischemia is one of the leading cause of disability in the world. Unfortunately, to this date there is no effective therapeutic strategy to promote neurological recovery among AIS survivors. Here we will discuss recent data indicating that binding of the serine proteinase urokinase-type plasminogen activator (uPA) to its receptor (uPAR) promotes synaptic repair in the ischemic brain, and will argue that this discovery has significant translational implications for the treatment of the rapidly growing number of patients that survive an AIS.