Hemofiltration-induced neuroprotection following ischemic stroke

Abstract

Ischemic stroke is accompanied by a three to four hundred percent increase in the brain’s extracellular fluid and cerebrospinal fluid glutamate concentration, which diffuses and damages surrounding neurons. In preclinical models of permanent middle cerebral artery occlusion, neurological outcomes correlate closely with blood or plasma glutamate levels. Previous attempts to reduce glutamate-induced excitotoxicity after stroke have included inhibition of glutamate receptors and administration of pyruvate and oxaloacetate. These strategies, including competitive and non-competitive glutamate receptor antagonists improved preclinical stroke outcomes but were without favorable outcomes or had significant unfavorable side-effects in human trials. We propose to decrease glutamate levels via an alternative mechanism, which should improve survival and neurological outcomes, without drug-induced side effects and complications. Glutamate, glutamate oxaloacetate transaminase and glutamate pyruvate transaminase concentrations are decreased during standard 4-hour long hemofiltration in chronic renal failure patients.