Malnutrition in Infancy as a Susceptibility Factor for Temporal Lobe Epilepsy in Adulthood Induced by the Pilocarpine Experimental Model

Abstract

Malnutrition during the earliest stages of life may result in innumerable brain problems. Moreover, this condition could increase the chances of developing neurological diseases, such as epilepsy. We analyzed the effects of early-life malnutrition on susceptibility to epileptic seizures induced by the pilocarpine model of epilepsy. Wistar rat pups were kept on a starvation regimen from day 1 to day 21 after birth. At day 60, 16 animals (8 = well-nourished; 8 = malnourished) were exposed to the pilocarpine experimental model of epilepsy. Age-matched well-nourished (n = 8) and malnourished (n = 8) rats were used as controls. Animals were video-monitored over 9 weeks. The following behavioral parameters were evaluated: first seizure threshold (acute period of the pilocarpine model); status epilepticus (SE) latency; first spontaneous seizure latency (silent period), and spontaneous seizure frequency during the chronic phase. The cell and mossy fiber sprouting (MFS) density were evaluated in the hippocampal formation. Our results showed that the malnourished animals required a lower pilocarpine dose in order to develop SE (200 mg/kg), lower latency to reach SE, less time for the first spontaneous seizure and higher seizure frequency, when compared to well-nourished pilocarpine rats. Histopathological findings revealed a significant cell density reduction in the CA1 region and intense MFS among the malnourished animals. Our data indicate that early malnutrition greatly influences susceptibility to seizures and behavioral manifestations in adult life. These findings suggest that malnutrition in infancy reduces the threshold for epilepsy and promotes alterations in the brain that persist into adult life.

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

“…Regarding the pilocarpine/malnutrition interaction, Cabral et al (2011) reported that malnourished rats require a lower pilocarpine dose to become epileptic in comparison with well-nourished animals, suggesting that malnutrition early in life reduces the threshold for pilocarpine-induced epilepsy. Our CSD findings using a sub-convulsing dose of pilocarpine are consistent with these findings (see Figure 4).…”

Early life maternal separation stress augmentation of limbic epileptogenesis: The role of corticosterone and HPA axis programming

“…We used MET (2-methyl-1,2-di-3-pyridyl-1-propanone, Sigma-Aldrich) to block the activity of 11β-hydroxylase, the enzyme responsible for the conversion of deoxycorticosterone to corticosterone, thereby preventing corticosterone synthesis (Temple and Liddle, 1970). This drug has been previously shown to efficiently block stress-induced rises in corticosterone (Calvo, et al, 1998). One hour prior to each kindling stimulation, rats received a 2mL/kg injection of MET (50mg/kg SC, dissolved in 2.5% ethanol and 97.5% saline), or vehicle (n=4/group).…”

“…Early life stress, a strong risk factor implicated in several psychiatric disorders (Gunnar and Quevedo, 2007), may serve as a common causal or contributory factor for MTLE and the psychopathologies that are often comorbid with the epilepsy (Hermann, et al, 2008;Kanner, 2009;Kanner, 2012). In the last decade, a consistent body of experimental research has provided evidence to support this theory, documenting an enduring increase in vulnerability to epileptogenesis following early postnatal stress (Huang, et al, 2002;Lai, et al, 2006;Salzberg, et al, 2007;Gilby, et al, 2009;Jones, et al, 2009;Lai, et al, 2009;Cabral, et al, 2011;Kumar, et al, 2011). Research into the biological mechanisms underlying this relationship, however, remains sparse (Koe, et al, 2009;Kumar, et al, 2011).…”