Progression of neuronal damage after status epilepticus and during spontaneous seizures in a rat model of temporal lobe epilepsy

In vitro status epilepticus but not spontaneous recurrent seizures cause cell death in cultured hippocampal neurons

“…In fact, aside from the cell death associated with the initial exposure to low Mg 2+ , there was no increase in neuronal cell death in cultures manifesting SREDs compared to age-matched control cultures for the life of the neurons in culture. The results are consistent with animal and human data that demonstrate that the majority of neuronal cell death is associated with SE and not with recurrent seizures (Duncan, 2002;Fujikawa, 2005;Fujikawa et al, 2000;Gorter et al, 2003;Holmes, 2002;Pitkanen et al, 2002). To our knowledge this study provides the first direct evidence in an in vitro model that continuous electrographic epileptiform activity is directly correlated with neuronal cell death in the absence of any other extracellular environmental effects on neuronal viability.…”

“…In vivo studies utilizing rat models of SE-induced temporal lobe epilepsy suggest that neuronal cell death is only associated with the initial injury from SE, but not with the subsequent spontaneous recurrent seizures (Gorter et al, 2003;Pitkanen et al, 2002); however, there is data showing that even a few evoked seizures in kindled rats produce TUNEL-positive hippocampal in hilar neurons (Bengzon et al, 1997) and hippocampal neuronal loss that increases with increasing numbers of kindled seizures (Cavazos et al, 1994). Clinical studies have demonstrated conflicting results with reports of increased serum and CSF levels of neuron-specific enolase, a marker of neuronal injury, after spontaneous seizures (Buttner et al, 1999).…”

“…Conversely, it is now widely accepted in animals and man that spontaneous recurrent seizures, occurring in the context of intractable epilepsy, do not cause significant brain injury (Fujikawa, 2005). Evidence is now accumulating especially from the in vivo models of epilepsy, suggesting that neuronal cell death is associated with initial epileptogenic insult and not with later spontaneous seizures (Gorter et al, 2003;Pitkanen et al, 2002). Understanding the effects of epileptiform discharges on neuronal viability is important in developing therapeutic strategies for treating SE and epilepsy.…”

Epileptogenesis

“…Many studies, however, have provided evidence that the frequency and severity of SRSs continue to increase after the first unprovoked or spontaneous seizure Cornett 1993, 1994;Hellier et al 1998;Nissinen et al 2000;Williams et al 2009;Kadam et al 2010), thus suggesting that epileptogenesis is a continuous and prolonged process. Furthermore, various forms of molecular and cellular plasticity, which are proposed to lead to the occurrence of the first unprovoked seizure, also continue indefinitely beyond the initial unprovoked seizure(s), and, thus, may contribute to the progression of the epileptic condition (for reviews, see Pitkänen et al 2002;Rakhade and Jensen 2009;Staley 2011, 2012;Pitkänen and Lukasiuk 2011). Many clinical studies have also independently suggested that human temporal lobe epilepsy, in particular, is progressive (Engel 1996(Engel , 2005(Engel , 2008Berg and Engel 2006).…”

Surgical and postmortem pathology studies: contribution for the investigation of temporal lobe epilepsy

“…This condition has been named "paradoxical TLE" 18 . There is enough data from animal models 19 and human studies 20,21 to affirm that prolonged seizures and status epilepticus may injury the hippocampus and eventually lead to MTS. However, in humans, MTS is not the inevitable consequence of repeated seizures and the exact time course of the relation between MTS and the occurrence of seizures is not precisely defined 5 .…”