Perinatal cerebral hypoxia-ischemia (HI) is an important cause of mortality and neurological disabilities such as cerebral palsy, epilepsy, and mental retardation. The potential for neuroprotection in HI can be achieved mainly during the recovery period. In previous work, we demonstrated that guanosine (Guo) prevented the decrease of glutamate uptake by hippocampal slices of neonatal rats exposed to a hypoxic-ischemic (HI) insult in vivo when administrated before and after insult. In the present study, we compared the effect of Guo administration only after HI using various protocols. When compared with the control, a decrease of [(3)H] glutamate uptake was avoided only when three doses of Guo were administered immediately, 24 h and 48 h after insult, or at 3 h, 24 h, and 48 h after injury or at 6 h, 24 h, and 48 h after HI. These findings indicate that early Guo administration (until 6 h) after HI, in three doses may enhance glutamate uptake into brain slices after hypoxia/ischemia, probably resulting in decreased excitotoxicity.
In nervous tissue, the calcium (Ca(2+)) release induces neurotransmitter exocytosis and synaptic plasticity in neurons and is essential for Ca(2+) waves and oscillations in astrocytes. In this work, we have investigated the effect of organocalchogens on calcium influx in synaptosomal preparations under basal and depolarizing conditions. Acute administration of ebselen caused a significant increase of 34% (p < 0.05) Ca(2+) influx, when under basal conditions but showed no effect on potassium stimulated calcium conditions by brain synaptosomes. Diphenyl ditelluride (PhTe)(2) increased (45)Ca(2+) influx by 40% (p < 0.05) under depolarizing conditions, while diphenyl diselenide (PhSe)(2) had no effect on the brain synaptosomes studied. In addition, we characterized an "in vitro" model with the purpose of studying Ca(2+) movements in slices. In this model, we examined the effect of diorganylchalcogenides using brain hippocampal slices, which showed the decrease of calcium influx with the three drugs studied. These findings showed that there are different effects of diorganylchalcogenides in the different models evaluated. It is possible that these differential effects result from the action of neural signal transduction pathways at different levels, possibly involving neurotransmitter release and channel targeting.
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