Differences in Evolution of Epileptic Seizures and Topographical Distribution of Tissue Damage in Selected Limbic Structures Between Male and Female Rats Submitted to the Pilocarpine Model

Abstract

Epidemiological evidence shows that clinical features and comorbidities in temporal lobe epilepsy (TLE) may have different manifestations depending on the sex of patients. However, little is known about how sex-related mechanisms can interfere with the processes underlying the epileptic phenomenon. The findings of this study show that male rats with epilepsy in the pilocarpine model have longer-lasting and more severe epileptic seizures, while female rats have a higher frequency of epileptic seizures and a greater number of seizure clusters. Significant sex-linked pathological changes were also observed: epileptic brains of male and female rats showed differences in mass reduction of 41.8% in the amygdala and 18.2% in the olfactory bulb, while loss of neuronal cells was present in the hippocampus (12.3%), amygdala (18.1%), and olfactory bulb (7.5%). Another important sex-related finding was the changes in non-neuronal cells with increments for the hippocampus (36.1%), amygdala (14.7%), and olfactory bulb (37%). Taken together, our study suggests that these neuropathological changes may underlie the differences in the clinical features of epileptic seizures observed in male and female rats.

Respiratory dysfunction in two rodent models of chronic epilepsy and acute seizures and its link with the brainstem serotonin system

“…Because we were using Sprague–Dawley rats from Envigo Laboratories, we had to monitor the time of onset of spontaneous recurrent seizures (SRSs) in our experiments. To determine whether rats were in the chronic phase of epilepsy, they were manipulated daily between 09:00 and 11:00 a.m. to define the onset of handling-induced seizures (HIS), which was induced by restraining rats at the level of the chest with gentle pressure for 10 s 9 , 52 . HIS were used in our study to help experimenters to define the time to start detecting the first behavioural spontaneous recurrent seizures (SRSs).…”

“…Epilepsy following pilocarpine-induced status epilepticus (Pilo-SE) in rats is one of the most studied models of TLE. Like patients with TLE, rats that became epileptic after Pilo-SE are notably characterized by chronic, spontaneous, and drug-resistant seizures 7 – 9 . Respiratory function of such rats has been studied previously after the onset of epilepsy and independent of seizure activity.…”

Sex and estrous cycle stage shape left-right asymmetry in chronic hippocampal seizures in mice

“…28 In another study, male rats treated systemically with pilocarpine developed longer lasting seizures over a period of several months, whereas female rats tended to have higher frequency of seizures. 29 In a systemic kainic acid injection model of TLE, male rats had greater susceptibility to seizures than their female counterparts. 28 In mice, however, the results regarding systemic KA injection have been mixed, with one study reporting higher mortality rates, more severe seizures, and increased neurodegeneration in females, 30 but another study describing higher mortality, seizure severity, cognitive impairment, hippocampal neuron loss, and reactive gliosis in males.…”

Long‐term ANT‐DBS effects in pilocarpine‐induced epileptic rats: A combined 9.4T MRI and histological study

“…In addition, this study did not perform histological analysis of other brain regions, which would be particularly interesting in epileptic rats with general damage. Moreover, there were significant differences in the patterns of SRS and hippocampal neuronal damage between male and female rats in the TLE model (Matovu & Cavalheiro, 2022). Female rats with TLE showed increased estradiol release and reduced progesterone withdrawal, and the hormonal environment played a significant role in sex‐linked differences and related brain damage (Amado & Cavalheiro, 1998).…”