The cellular mechanisms underlying the neuroprotective action of the immunosuppressant FK506 in experimental stroke remain uncertain, although in vitro studies have implicated an antiexcitotoxic action involving nitric oxide and calcineurin. The present in vivo study demonstrates that intraperitoneal pretreatment with 1 and 10 mg/kg FK506, doses that reduced the volume of ischemic cortical dama...

Prolonged activation of glutamate receptors leads to excitotoxicity. Several processes such as reactive oxygen species (ROS) production and activation of the calcium-dependent protease, calpain, contribute to glutamate-induced damage. It has been suggested that the ROS-producing enzyme, NADPH oxidase (NOX), plays a role in excitotoxicity. Studies have reported NOX activation after NMDA receptor...

Overactivation of subtype P2X7 receptors can induce excitotoxic neuronal death by calcium (Ca(2+)) overload. In this study, we characterize the functional properties of P2X7 receptors using electrophysiology and Ca(2+) monitoring in primary cortical neuron cultures and in brain slices. Both electrical responses and Ca(2+) influx induced by ATP and benzoyl-ATP were reduced by Brilliant Blue G (B...

Lurcher is a spontaneous mouse mutant characterized by premature and aberrant apoptosis in the cerebellum. The phenotype has been shown to be caused by a point mutation in the delta2 glutamate receptor subunit gene that results in a large constitutive inward current, which has proved that endogenous excitotoxicity can lead to apoptotic cell death. Additional studies have suggested a direct link...

Nitric oxide (NO) has a critical role in neuronal function; however, high levels lead to cellular injury. While guanidino-methylated arginines (MA) including asymmetric dimethylarginine (ADMA) and N(G)-methyl-l-arginine (NMA) are potent competitive inhibitors of nitric oxide synthase (NOS) and are released upon protein degradation, it is unknown whether their intracellular concentrations are su...

Overstimulation of ionotropic glutamate receptors causes excitotoxic neuronal death contributing to neurodegenerative disorders. Massive influx of calcium in excitotoxicity provokes alterations in the membrane potential of mitochondria and increases the production of reactive oxygen species. Here we report that Mangifera indica L. extracts (MiE) prevent glutamate-induced excitotoxicity in prima...

The role of carnosine, N-acetylcarnosine and homocarnosine as scavengers of reactive oxygen species and protectors against neuronal cell death secondary to excitotoxic concentrations of kainate and N-methyl-d-aspartate was studied using acutely dissociated cerebellar granule cell neurons and flow cytometry. We find that carnosine, N-acetylcarnosine and homocarnosine at physiological concentrati...

The pathogenesis of stroke, trauma and chronic degenerative diseases, such as Alzheimer's disease (AD), has been linked to excitotoxic processes due to inappropriate stimulation of the N-methyl-D-aspartate receptor (NMDA-R). Attempts to use potent competitive NMDA-R antagonists as neuroprotectants have shown serious side-effects in patients. As an alternative approach, we were interested in the...