Yeungnam Univ J Med.  2018 Dec;35(2):192-198. 10.12701/yujm.2018.35.2.192.

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

• Kim JY
• Kim JH
• Lee HJ
• Kim SH
• Jung YJ
• Lee HY
• Kim HJ
• Kim SY

• KMID: 2433738
• DOI: http://doi.org/10.12701/yujm.2018.35.2.192

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.

Keyword

Electroencephalography; High voltage sharp wave; Intrahippocampal kainic acid model; Red ginseng; Temporal lobe epilepsy

MeSH Terms

Animals
Blood Urea Nitrogen
Brain
Electrodes, Implanted
Electroencephalography*
Epilepsy, Temporal Lobe*
Hippocampus
Immune System
Immunohistochemistry
Inflammation
Kainic Acid*
Liver Function Tests
Mice
Models, Animal
Panax*
Seizures
Status Epilepticus
Temporal Lobe*
Valproic Acid
Kainic Acid
Valproic Acid

Figure

• 

  Fig. 1. Histological findings of the hippocampus after intrahippocampal kainic acid injection. There is no difference in pyramidal cell damage between valproic acid group (A) and red ginseng group (B) (hematoxylin and eosin stain, ×100). Glial fibrillary acidic protein-positive astrocytes are more common in valproic acid group (C) than in red ginseng group (D) (immunohistochemical stain, ×100).

• 

  Fig. 2. Weekly continuous EEG monitorings following intrahippocampal injection of KA in male mice. The EEG recordings were performed via depth and cortical electrodes (A). Electroencephalographic findings during status epilepticus, characterized by spikes, polyspikes and spike-wave complexes. Two-thirds of the mice showed generalized seizures. (B-D) showed high-voltages sharp waves and multiple spikes in 1, 2, and 4 weeks after KA injection. EEG, electroencephalography; KA, kainic acid.

• 

  Fig. 3. Anticonvulsant effects of VPA and RG in IHKA animal model by EEG. Epileptic activity was recorded from the depth and cortical electrodes after KA injection at right CA3 region of the dorsal hippocampus. The graph shows the number of HVSWs frequency per hour weekly for 4 weeks. Overall, the number of HVSWs decreased with time, and there was no difference between the two groups (p=0.486). VPA, valproic acid; RG, red ginseng; IHKA, intrahippocampal kainic acid; EEG, electroencephalography; KA, kainic acid; HVSWs, high-voltages sharp waves.

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