Pilocarpine/ascorbic acid interaction in the immature brain: Electrophysiological and oxidative effects in well-nourished and malnourished rats

Abstract

Ascorbic acid (AA) administration has been associated with neuroprotection against oxidative stress, although at high doses it can facilitate oxidation and acts like a proconvulsing drug. The pilocarpine-induced epilepsy model has been widely studied. However, less is known about the effects of sub-convulsive doses of pilocarpine on brain activity in immature animals under normal or deficient nutritional conditions. Herein, we investigated the effects of chronic pilocarpine administration in a sub-convulsive dose, with or without AA, on the excitability-related phenomenon denominated as cortical spreading depression (CSD) and levels of lipid peroxidation-induced malondialdehyde in well-nourished and malnourished rats. At postnatal days 7-28, rats received no gavage treatment (naïve group), saline (vehicle group), 45 mg/kg/d of pilocarpine and/or 120 mg/kg/d of AA. CSD propagation and malondialdehyde levels were analyzed at 34-40 days. The pilocarpine group presented with lower CSD velocities, while AA groups exhibited higher CSD velocities and augmented malondialdehyde levels compared with controls. The co-administration of AA partially antagonized the pilocarpine CSD effects, but did not revert it to control levels. Malnutrition increased CSD amplitude and velocity in comparison to the well-nourished condition. The electrocorticogram (ECoG) amplitude increased after CSD (ECoG potentiation) when compared with the baseline amplitude before CSD. However, no intergroup difference was observed in this CSD-related ECoG potentiation. The results support the hypothesis of a pilocarpine/ascorbic acid interaction in the immature rat brain and might help further the understanding of this interaction on neuronal electrical activity and oxidative stress.

Valeriana officinalis Counteracts Rotenone Effects on Spreading Depression in the Rat Brain in vivo and Protects Against Rotenone Cytotoxicity Toward Rat Glioma C6 Cells in vitro

“…This finding confirms previous data indicating that substances with anticonvulsant activity (e.g., dipyrone; Doretto et al, 1998 ) enhance the CSD velocity ( Amaral et al, 2009 ). Moreover, these data are similar to previous findings showing that low and high doses of the antioxidant vitamin ascorbic acid decelerated and accelerated CSD, respectively, in rats ( Mendes-da-Silva et al, 2014 , 2018 ). Taken together, these findings are in accordance with the idea that the CSD, as an interesting phenomenon, can help in extending our knowledge about the involvement of redox imbalance into the pathogenesis of neurological diseases ( Guedes et al, 2012 ) with the possible involvement of astrocytes ( Torrente et al, 2014 ).…”

Taurine/Pilocarpine Interaction in the Malnourished Rat Brain: A Behavioral, Electrophysiological, and Immunohistochemical Analysis

“…The present study extends the previous observations of our group on the effects of taurine (Francisco and Guedes, 2015) and pilocarpine (Mendes-da-Silva et al, 2018) in rats of a younger age (PND7-27) than our rats (PND35-55). Analyzing such effects at another age might be of importance, regarding the time course of drug actions (Guedes and Abadie-Guedes, 2019).…”

“…and gavage; n = 10 L 9 and 8 L 15 rats); (3) Taurine (300 mg/kg/day via gavage; n = 9 L 9 and 9 L 15 rats), as previously described (Francisco and Guedes, 2015); (4) Pilocarpine (45 mg/kg/day via i.p. ; n = 9 L 9 and 10 L 15 rats), following Mendes-da-Silva et al (2018); (5) Taurine plus pilocarpine (300 mg/kg/day via gavage and 45 mg/kg/day via i.p, respectively; n = 8 L 9 and 11 L 15 rats). Scopolamine methyl nitrate, a muscarinic receptor antagonist, was administered (1 mg/kg/day via i.p.)…”

“…Under this condition, no behavioral or electrocorticographic changes indicative of seizures were observed (Guedes and Vasconcelos, 2008). However, under subconvulsing paradigms several reports have described anxiety-like behavioral profiles (Duarte et al, 2014; Francisco and Guedes, 2018), reductions in glycemia (Francisco and Guedes, 2018), increases in brain oxidative stress (Mendes-da-Silva et al, 2018) and impairment of propagation of the excitability-related phenomenon known as cortical spreading depression (CSD) along the cortical rodent tissue (Francisco and Guedes, 2018; Mendes-da-Silva et al, 2018).…”

Brain Aging and Electrophysiological Signaling: Revisiting the Spreading Depression Model

“…More recently, we demonstrated that the non-carotenoid antioxidant alpha-tocopherol also antagonizes the effect of ethanol on CSD, suggesting that this antagonistic action is not a particular property of carotenoids (Abadie-Guedes et al, 2016). In line with this suggestion, it is interesting to note that another non-carotenoid antioxidant molecule, ascorbic acid, has been shown to modulate CSD (Mendes-da-Silva et al, 2014, 2018).…”