Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2018 Sep;145:93-101.
doi: 10.1016/j.eplepsyres.2018.06.009. Epub 2018 Jun 18.

Inverted-U Response of Lacosamide on Pilocarpine-Induced Status Epilepticus and Oxidative Stress in C57BL/6 Mice Is Independent of Hippocampal Collapsin Response Mediator protein-2

Affiliations

Inverted-U Response of Lacosamide on Pilocarpine-Induced Status Epilepticus and Oxidative Stress in C57BL/6 Mice Is Independent of Hippocampal Collapsin Response Mediator protein-2

Nikita Nirwan et al. Epilepsy Res. .

Abstract

Objective: Currently, lacosamide (LCM) is not approved for use in status epilepticus (SE) but several shreds of evidence are available to support its use. The present study was, therefore, undertaken to evaluate the effect of LCM on pilocarpine (PILO) induced SE and neurodegeneration in C57BL/6 mice and to ascertain the involvement of CRMP-2 in mediating above effect.

Methods: Pilocarpine-induced SE model was developed to explore the effect of LCM 20, 40 and 80 mg/kg in mice. We assessed the seizure severity, seizure latency, spontaneous alternation behavior (SAB) and motor coordination by behavioral observation. Histopathological evaluation and measurement of the levels of CRMP-2, reduced glutathione (GSH) and malondialdehyde (MDA) were carried out in mice hippocampus.

Results: LCM exhibited a biphasic effect i.e., protection against SE at 20 mg/kg and 40 mg/kg dose whilst aggravated seizure-like behavior and mortality at 80 mg/kg. Further, it increased percentage alternation (i.e., restored spatial memory) in SAB and elevated motor impairment with increasing dose. Histologically, LCM 20 mg/kg and 40 mg/kg (but not 80 mg/kg) reduced neurodegeneration. LCM 20 mg/kg and 40 mg/kg reversed the elevated MDA and GSH levels while 80 mg/kg showed a tendency to increase oxidative stress. In contrast, LCM (at all doses) reversed the pilocarpine-induced elevation of collapsin response mediator protein-2 (CRMP-2).

Conclusion: LCM protected against pilocarpine-induced SE, associated neurodegeneration and improved pilocarpine-associated impairment of spatial memory. The study reveals that CRMP-2 may not be mediating the inverted-U-response of LCM at least in pilocarpine model. Therefore, the anti-oxidant effect of LCM (and not its ability to modulate CRMP-2) was anticipated as the mechanism underlying neuroprotection.

Keywords: CRMP-2; Lacosamide; Oxidative stress; Pilocarpine; Spatial memory; Status epilepticus.

Similar articles

See all similar articles

Cited by 2 articles

Publication types

MeSH terms

LinkOut - more resources

Feedback