Long lasting behavioral and electrophysiological action of early administration of guanosine: Analysis in the adult rat brain.

Guanosine (GUO) is a guanine-based purine that has been extensively described in the literature as an endogenous nucleoside with participation in brain cell signalling pathways. Here, we evaluated whether chronic treatment with exogenous guanosine during brain development altered behavioral and electrophysiological parameters in adulthood. Rat pups received a daily intraperitoneal injection of 10, 50 or 100 mg/ kg/day GUO, or saline solution or no treatment (naive group) from postnatal (P) day 7 to P27. At P 60-65 the animals were behaviorally tested in the Elevated Plus-Maze (EPM). On P90-100, the electrophysiological phenomenon known as cortical spreading depression (CSD) was recorded on the right cortical surface for 4 h. With the EPM task, GUO treatment was associated with a significant increase in rearing behavior and a non-significant trend towards anxiogenic behavior. In a dose-dependent manner, GUO significantly (p < 0.01) increased weight gain on P90, and reduced the CSD propagation velocity from 3.42 ±â€¯0.10 and 3.43 ±â€¯0.10 mm/min in the Naive and Vehicle controls, respectively, to 3.05 ±â€¯0.12 mm/min, 2.87 ±â€¯0.07 mm/min and 2.25 ±â€¯0.25 mm/min in the groups treated with 10, 50 and 100 mg/kg/d GUO, respectively. The results confirmed the hypothesis that the chronic treatment with GUO early in life modulates CSD and body weight. Data on CSD propagation suggest that, besides its suppressing action on glutamatergic transmission (via enhancement of astrocytic glutamate uptake), GUO might act as an antioxidant in the brain, a hypothesis that deserves further exploration.

Safflower (Carthamus tinctorius L.) oil during pregnancy and lactation influences brain excitability and cortex oxidative status in the rat offspring.

OBJECTIVES: To evaluate how safflower oil (SFO) influences brain electrophysiology and cortical oxidative status in the offspring, mothers received a diet with SFO during brain development period. METHODS: Beginning on the 14th day of gestation and throughout lactation, rats received safflower (safflower group - SG) or soybean oil (control group - CG) in their diet. At 65 days old, cortical spreading depression (CSD) and cortex oxidative status were analyzed in the offspring. RESULTS: SG presented reduction of the CSD velocity as compared to the CG (SG: 3.24 ± 0.09; CG: 3.37 ± 0.07 mm/min). SFO reduced levels of lipid peroxidation by 39.4%. SG showed the following increases: glutathione-S-transferase, 40.8% and reduced glutathione, 34.3%. However, SFO decreased superoxide dismutase by 40.4% and catalase by 64.1%. To control for interhemispheric effects, since CSD was recorded only in the right cortex, we evaluated the oxidative status in both sides of the cortex; no differences were observed. DISCUSSION: Data show that when SFO is consumed by the female rats during pregnancy and lactation, the offspring present long-term effects on brain electrophysiology and cortical oxidative state. The present study highlights the relevance of understanding the SFO intake of pregnant and lactating mammals.

Neonatal dexamethasone accelerates spreading depression in the rat, and antioxidant vitamins counteract this effect.

The use of dexamethasone (Dex) to treat chronic lung disease in preterm infants may produce adverse effects in the developing brain. Here, we evaluated the effects of neonatal Dex on the propagation of cortical spreading depression (CSD), and tested the action of vitamins C and E against the effect of Dex. Five groups of Wistar rats received, respectively: [1] no treatment (Naïve); [2] Vehicle (V); [3] tapering doses of Dex (Dex; 0.5mg/kg, 0.3mg/kg, and 0.1mg/kg) on postnatal day (PND) 1-3; [4] Dex plus 200mg/kg vitamin C and 100mg/kg vitamin E (DexCE); [5] only vitamins C and E (CE). Vehicle and vitamins were administered on PND 1-6. CSD was recorded after the pups reached maturity (PND 60-70). The Dex-treated group presented with higher CSD velocities (mean values ± SD, in mm/min: 4.14 ± 0.22, n=10) compared with the control groups (Naïve: 3.52 ± 0.13, n=8; V: 3.57 ± 0.18, n=10; CE: 3.51 ± 0.24, n=10; p<0.05 for all). Vitamins C and E antagonized this effect (DexCE group; CSD velocity: 3.43 ± 0.12, n=9). No intergroup difference was observed concerning P-wave amplitude and duration. In all groups, after the cortex underwent CSD, the electrocorticogram (ECoG) amplitude increased approximately 50% compared with the baseline amplitude for the same animal (CSD-induced ECoG potentiation); however, no intergroup difference was observed. Data suggest that coadministration of antioxidant vitamins with Dex may be a helpful therapeutic strategy to reduce brain adverse effects of dexamethasone.

Prooxidant versus antioxidant brain action of ascorbic acid in well-nourished and malnourished rats as a function of dose: a cortical spreading depression and malondialdehyde analysis.

Although ascorbic acid (AA) is an antioxidant, under certain conditions it can facilitate oxidation, which may underlie the opposite actions of AA on brain excitability in distinct seizure models. Here, we investigated whether chronic AA administration during brain development alters cortical excitability as a function of AA dose, as indexed by cortical spreading depression (CSD) and by the levels of lipid peroxidation-induced malondialdehyde. Well-nourished and early-malnourished rats received per gavage 30, 60, or 120 mg/kg/d of AA, saline, or no gavage treatment (naïve group) at postnatal days 7-28. CSD propagation and malondialdehyde levels were analyzed at 30-40 days. Confirming previous observations, CSD velocities were significantly higher in the early-malnourished groups than in the well-nourished groups. AA dose was important: 30 mg/kg/d AA decelerated CSD and reduced malondialdehyde levels, whereas 60 mg/kg/d and 120 mg/kg/d accelerated CSD and augmented malondialdehyde levels compared with the corresponding saline and naïve groups. Our findings reinforce previous suggestion that AA acts as an antioxidant in the brain when administered at low doses, but as a prooxidant at high doses, as indicated by CSD propagation and malondialdehyde levels.