Ischemic stroke is a devastating condition, for which there is still no effective therapy. Acute ischemic stroke is associated with high concentrations of glutamate in the blood and interstitial brain fluid. The inability of the tissue to retain glutamate within the cells of the brain ultimately provokes neuronal death. Increased concentrations of interstitial glutamate exert further excitotoxic effects on healthy tissue surrounding the infarct zone. We developed a strategy based on peritoneal dialysis to reduce blood glutamate levels, thereby accelerating brain-to-blood glutamate clearance. In a rat model of stroke, this simple procedure reduced the transient increase in glutamate, consequently decreasing the size of the infarct area. Functional magnetic resonance imaging demonstrated that the rescued brain tissue remained functional. Moreover, in patients with kidney failure, peritoneal dialysis significantly decreased glutamate concentrations. Our results suggest that peritoneal dialysis may represent a simple and effective intervention for human stroke patients.
María del Carmen Godino, Victor G. Romera, José Antonio Sánchez-Tomero, Jesus Pacheco, Santiago Canals, Juan Lerma, José Vivancos, María Angeles Moro, Magdalena Torres, Ignacio Lizasoain, José Sánchez-Prieto
Peritoneal dialysis attenuates ischemia-induced increases in plasma glutamate concentration and cerebral infarct size.