Psychiatry Investig.  2017 Nov;14(6):844-850. 10.4306/pi.2017.14.6.844.

The Mechanism of Anti-Epileptogenesis by Levetiracetam Treatment is Similar to the Spontaneous Recovery of Idiopathic Generalized Epilepsy during Adolescence

• Kikuyama H
• Hanaoka T
• Kanazawa T
• Yoshida Y
• Mizuno T
• Toyoda H
• Yoneda H

• KMID: 2402413
• DOI: http://doi.org/10.4306/pi.2017.14.6.844

Abstract

OBJECTIVE
The anti-epileptogenic drug levetiracetam has anticonvulsant and anti-epileptogenesis effects. Synergy between cell death and inflammation can lead to increased levels of apoptosis inhibitory factors and brain-derived neurotrophic factor, aberrant neurogenesis and extended axon sprouting. Once hyperexcitation of the neural network occurs, spontaneous seizures or epileptogenesis develops. This study investigated whether the anti-epileptogenic effect of levetiracetam is due to its alternate apoptotic activity.
METHODS
Adult male Noda epileptic rats were treated with levetiracetam or vehicle control for two weeks. mRNA quantification of Bax, Bcl-2 and GAPDH expression were performed from prefrontal cortex and hippocampus tissue samples.
RESULTS
The levetiracetam-treated group showed a significant increase of Bax/Bcl-2 mRNA expression ratio in the prefrontal cortex than the control group, but no change in the Bax/Bcl-2 mRNA expression ratio in hippocampus.
CONCLUSION
Idiopathic generalized epilepsy including childhood absence epilepsy develop at childhood and recover spontaneously during adolescence. The aberrant neural excitable network is pruned by a neural-maturing action. This study suggests the mechanism of acquired anti-epileptogenesis by levetiracetam treatment may be similar to spontaneous recovery of idiopathic generalized epilepsy during adolescence.

Keyword

Levetiracetam; Apoptosis; Epileptogenesis; Idiopathic generalized epilepsy; Noda epileptic rat

MeSH Terms

Adolescent*
Adult
Animals
Apoptosis
Axons
Brain-Derived Neurotrophic Factor
Cell Death
Epilepsy, Absence
Epilepsy, Generalized*
Hippocampus
Humans
Inflammation
Male
Neurogenesis
Prefrontal Cortex
Rats
RNA, Messenger
Seizures
Brain-Derived Neurotrophic Factor
RNA, Messenger