Modulation of leukotriene D4 attenuates the development of seizures in mice

Ashish K. Rehni, Thakur Gurjeet Singh

Research output: Contribution to journalArticlepeer-review

21 Scopus citations

Abstract

The present study has been designed to pharmacologically investigate the effect of Montelukast sodium, a leukotriene D4 receptor antagonist, and 1,2,3,4, tetrahydroisoquinoline, a leukotriene D4 synthetic pathway inhibitor, on the pathophysiological progression of seizures using mouse models of kindled epilepsy and status epilepticus induced spontaneous recurrent seizures. Pentylenetetrazole (40mgkg-1) (PTZ) administration every second day for a period of 15d was used to elicit chemically induced kindled seizure activity in mice. In a separate set of groups, fifty consecutive electroshocks were delivered to mice using corneal electrodes with continuously increasing intensity with an inter-shock interval of 40s. Severity of kindled seizures was assessed in terms of a composite kindled seizure severity score (KSSS). Pilocarpine (100mgkg-1) was injected every twenty minutes until the onset of status epilepticus. A spontaneous recurrent seizure severity score (SRSSS) was recorded as a measure of quantitative assessment of the progressive development of spontaneous recurrent seizures induced after pilocarpine status epilepticus. Sub-acute PTZ administration and electroshock induced the development of severe form of kindled seizures in mice. Severity of kindled seizures was assessed in terms of a composite kindled seizure severity score. Further, pharmacological status epilepticus elicited a progressive evolution of spontaneous recurrent seizures in the animals. However, Montelukast sodium, a leukotriene D4 receptor antagonist, as well as 1,2,3,4, tetrahydroisoquinoline, a leukotriene D4 synthetic pathway inhibitor, markedly and dose dependently suppressed the development of kindled seizures as well as pilocarpine induced spontaneous recurrent seizures. Therefore, leukotriene D4 may be implicated in the pathogenesis of seizures.

Original languageEnglish (US)
Pages (from-to)97-106
Number of pages10
JournalProstaglandins Leukotrienes and Essential Fatty Acids
Volume85
Issue number2
DOIs
StatePublished - Aug 2011
Externally publishedYes

Keywords

  • 1,2,3,4, tetrahydroisoquinoline
  • Gamma glutamyl transpeptidase
  • Leukotriene D receptors
  • Montelukast sodium
  • Seizures

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Cell Biology

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