Antiepileptic and anti-neuroinflammatory effects of red ginseng in an intrahippocampal kainic acid model of temporal lobe epilepsy demonstrated by electroencephalography

Abstract

Background: Chronic inflammation can lower the seizure threshold and have influence on epileptogenesis. The components of red ginseng (RG) have anti-inflammatory effects. The abundance of peripherally derived immune cells in resected epileptic tissue suggests that the immune system is a potential target for anti-epileptogenic therapies. The present study used continuous electroencephalography (EEG) to evaluate the therapeutic efficacy of RG in intrahippocampal kainic acid (IHKA) animal model of temporal lobe epilepsy. Methods: Prolonged status epilepticus (SE) was induced in 7-week-old C57BL/6J mice via stereotaxic injection of kainic acid (KA, 150 nL; 1 mg/mL) into the right CA3/dorsal hippocampus. The animals were implanted electrodes and monitored for spontaneous seizures. Following the IHKA injections, one group received treatments of RG (250 mg/kg/day) for 4 weeks (RG group, n=7) while another group received valproic acid (VPA, 30 mg/kg/day) (VPA group, n=7). Laboratory findings and pathological results were assessed at D29 and continuous (24 h/week) EEG monitoring was used to evaluate high-voltage sharp waves on D7, D14, D21, and D28. Results: At D29, there were no differences between the groups in liver function test but RG group had higher blood urea nitrogen levels. Immunohistochemistry analyses revealed that RG reduced the infiltration of immune cells into the brain and EEG analyses showed that it had anticonvulsant effects. Conclusion: Repeated treatments with RG after IHKA-induced SE decreased immune cell infiltration into the brain and resulted in a marked decrease in electrographic seizures. RG had anticonvulsant effects that were similar to those of VPA without serious side effects.

Robust chronic convulsive seizures, high frequency oscillations, and human seizure onset patterns in an intrahippocampal kainic acid model in mice

“…We provide evidence of prolonged convulsive seizures similar to seizure durations reported in human TLE (Balish et al, 1991) and data from an Epilepsy Monitoring Unit (Jenssen et al, 2006). The longer-lasting seizures contrast with the 3-7 sec epileptiform abnormalities reported by some past studies of IHKA in mice (Kim et al, 2018; Sandau et al, 2019; Lai et al, 2020). In addition, our results differ from what appears to be continuous spiking at the site of IHKA injection indicated by some investigators (Sandau et al, 2019).…”

“…A study in the pilocarpine model suggested that single housing may increase seizures by a factor of 16 (Manouze et al, 2019). Single housing might thus explain why very frequent and brief (3-7 sec) epileptiform abnormalities have been reported in IHKA-treated mice in the past (Kim et al, 2018; Sandau et al, 2019; Lai et al, 2020; Rusina et al, 2021). It would be possible that our approach that included frequent handling combined with enriched housing reduced these very frequent abnormalities thereby allowing the expression of robust seizures.…”

“…EEG recordings from the site of IHKA injection showed that most frequent epileptiform abnormalities in mice were short-lasting non-convulsive episodes (Bouilleret et al, 1999; Maroso et al, 2011) which are not compelling seizures. Brief (3-7 sec) abnormalities were reported by others where they could be as frequent as 100 per hr (Kim et al, 2018; Sandau et al, 2019; Lai et al, 2020) which are also inconsistent with characteristics of seizures from an epileptic animal. Sometimes the EEG examples that were published suggested trains of spikes or epileptiform activity occurred in the wks after IHKA, but these are not clear seizures.…”

“…EEG recordings from the site of IHKA injection showed that most frequent epileptiform abnormalities in mice were short-lasting non-convulsive episodes (Bouilleret et al, 1999; Maroso et al, 2011). Brief (3-7 sec) abnormalities were reported by others where they could be as frequent as 100 per hr (Kim et al, 2018; Sandau et al, 2019; Lai et al, 2020). Sometimes the EEG examples that were published suggested trains of spikes or epileptiform activity occurred in the wks after IHKA, but seizures were either rare, not shown, or the evidence that they occurred was not strong (e.g., Kiasalari et al, 2016; Zhu et al, 2016; Runtz et al, 2018; Bielefeld et al, 2019; Li et al, 2020).…”

Robust chronic convulsive seizures, high frequency oscillations, and human seizure onset patterns in an intrahippocampal kainic acid model in mice

“…EEG recordings from the site of IHKA injection showed that most frequent epileptiform abnormalities in mice were short-lasting non-convulsive episodes ( Bouilleret et al, 1999 ; Maroso et al, 2011 ) which are not compelling seizures. Brief (3–7 s) abnormalities were reported by others where they could be as frequent as 100 per hr ( Kim et al, 2018 ; Sandau et al, 2019 ; Lai et al, 2020 ) which are also inconsistent with characteristics of seizures from an epileptic animal. Sometimes the EEG examples that were published suggested trains of spikes or epileptiform activity occurred in the wks after IHKA, but these are not clear seizures.…”