Maternal seizures can affect the brain developing of offspring

Abstract

To elucidate the impact of maternal seizures in the developing rat brain, pregnant Wistar rats were subjected to the pilocarpine-induced seizures and pups from different litters were studied at different ages. In the first 24 h of life, blood glucose and blood gases were analyzed. (14)C-leucine [(14)C-Leu] incorporation was used to analyze protein synthesis at PN1, and Western Blot method was used to analyze protein levels of Bax, Bcl-2 and Poly(ADP-ribose) polymerase-1 (PARP-1) in the hippocampus (PN3-PN21). During the first 22 days of postnatal life, body weight gain, length, skull measures, tooth eruption, eye opening and righting reflex have been assessed. Pups from naive mothers were used as controls. Experimental pups showed a compensated metabolic acidosis and hyperglycemia. At PN1, the [(14)C-Leu] incorporation into different studied areas of experimental pups was lower than in the control pups. During development, the protein levels of Bax, Bcl-2 and PARP-1 in the hippocampus of experimental pups were altered when compared with control pups. A decreased level of pro- and anti-apoptotic proteins was verified in the early postnatal age (PN3), and an increased level of pro-apoptotic proteins concomitant with a reduced level of anti-apoptotic protein was observed at the later stages of the development (PN21). Experimental pups had a delay in postnatal growth and development beyond disturb in protein synthesis and some protein expression during development. These changes can be result from hormonal alterations linked to stress and/or hypoxic events caused by maternal epileptic seizures during pregnancy.

Sub-Convulsing Dose Administration of Pilocarpine Reduces Glycemia, Increases Anxiety-Like Behavior and Decelerates Cortical Spreading Depression in Rats Suckled on Various Litter Sizes

“…In the present work, pilocarpine treatment of the pups did reduce the animals’ body weight (Figure 1) and their blood glucose levels (Figure 2). While the data on body weight are coherent, differences in the blood glucose levels could be attributed to distinct pilocarpine treatment paradigms: administration of convulsing doses to the mothers (Cossa et al, 2016) vs. treatment of the pups with sub-convulsing doses (present work).…”

“…Regarding the action of pilocarpine, previous work reported impairment in the growth and development as well as high blood glucose levels in pups of pilocarpine-treated epileptic dams (Cossa et al, 2016). In the present work, pilocarpine treatment of the pups did reduce the animals’ body weight (Figure 1) and their blood glucose levels (Figure 2).…”

“…Evidence suggests that epilepsy influences emotional responses in human beings (Devinsky, 2004; Jackson and Turkington, 2005), and anxiety has been the most common psychological disorder among people with epilepsy (Beyenburg et al, 2005). Pilocarpine-induced experimental epilepsy in rodents has been associated with glycemia, learning and memory disturbances and behavioral disorders such as depression and anxiety (Cardoso et al, 2009; Duarte et al, 2014; Castelhano et al, 2015; Cossa et al, 2016). Furthermore, although sub-convulsing doses of pilocarpine do not cause behavioral or electrocorticographic changes indicative of seizure, they are able to antagonize the propagation of the excitability-related phenomenon known as cortical spreading depression (CSD) along the cortical rodent tissue (Guedes and Vasconcelos, 2008).…”

“…However, the hypothesis that malnourished humans would present a higher incidence of epilepsy compared to well-nourished humans needs much investigation. Previous studies on well-nourished rats described significant effects of a convulsing dose of pilocarpine on body weight and glycemia (Cossa et al, 2016), as well as on the propagation of CSD (Guedes and Cavalheiro, 1997). However, it is not known whether this convulsing compound would act relevantly on behavioral and electrophysiological parameters, when chronically applied in very low sub-convulsing doses, i.e., when producing a situation of chronic muscarinic cholinergic activation.…”