Relationship between seizure frequency and number of neuronal and non-neuronal cells in the hippocampus throughout the life of rats with epilepsy

Abstract

The relationship between seizure frequency and cell death has been a subject of controversy. To tackle this issue, we determined the frequency of seizures and the total number of hippocampal cells throughout the life of rats with epilepsy using the pilocarpine model. Seizure frequency varied in animals with epilepsy according to which period of life they were in, with a progressive increase in the number of seizures until 180 days (sixth months) of epileptic life followed by a decrease (330 days-eleventh month) and subsequently stabilization of seizures. Cell counts by means of isotropic fractionation showed a reduction in the number of hippocampal neuronal cells following 30, 90, 180 and 360 days of spontaneous recurrent seizures (SRS) in rats compared to their controls (about 25%-30% of neuronal cell reduction). In addition, animals with 360 days of SRS showed a reduction in the number of neuronal cells when compared with animals with 90 and 180 days of seizures. The total number of hippocampal non-neuronal cells was reduced in rats with epilepsy after 30 days of SRS, but no significant alteration was observed on the 90th, 180th and 360th days. The total number of neuronal cells was negatively correlated with seizure frequency, indicating an association between occurrence of epileptic seizures throughout life and neuronal loss. In sum, our results add novel data to the literature concerning the time-course of SRS and hippocampal cell number throughout epileptic life.

Volume change in amygdala enlargement as a prognostic factor in patients with temporal lobe epilepsy: A longitudinal study

“…In this regard, AE observed in Group B may be a transient secondary change developed after exposure to recurrent seizures, and faster volume reduction may be a resolution process of AE. Accumulating evidence suggests that seizure‐induced changes could also be caused by recurrent seizures, especially in structures susceptible to damage (eg, hippocampus or amygdala), although the degree of these changes is generally modest compared to changes induced by status epilepticus . Intriguingly, the neuronal injury affected by seizures do not necessarily result in volume loss, but may also result in hypertrophic changes instead .…”

“…These findings can be interpreted threefold. First, based on our hypothesis that AE may be attributed to seizure‐induced change, AE in patients with low‐frequency seizures may have been less affected by seizures, thereby leaving less to be resolved after seizure control . Second, the relatively slow APCEAV may be indicative of relatively modest treatment response.…”

“…Despite the growing interest in TLE‐AE, whether AE serves as a potential epileptogenic substrate remains elusive. Moreover, whether a lesion located in the epileptogenic zone may be a cause or a consequence of seizures, or even both, is one of the unresolved conundrums in focal epilepsy . Considering that TLE‐AE patients often present AE as their only structural abnormality and that most of them present epileptiform discharges ipsilateral to the enlarged amygdala (EA), AE is increasingly recognized as a convincing epileptogenic substrate .…”

“…Moreover, several studies have reported that AE tends to improve when seizures are adequately controlled, suggesting that AE might be a seizure‐induced change at least in a subset of patients. In this regard, the degree of AE changes may be related to seizure frequency, considering that seizure‐induced alteration such as cell swelling is more likely to develop when exposed to frequent seizures …”

Systemic evidence of acute seizure-associated elevation in serum neuronal injury biomarker in patients with temporal lobe epilepsy

“…In experimental models of epilepsy, induction of status epilepticus, not surprisingly, leads to hippocampal neuron loss [11]. However, spontaneously recurring seizures in such models are also associated with neuronal loss [12], suggesting that individual seizures may induce neurodegeneration. In humans, neuronal injury induced by trauma, hypoxia, and stroke can be detected by measuring levels of neuron-specific enolase (NSE) in serum [13].…”