Pharmacological inhibition of inducible nitric oxide synthase attenuates the development of seizures in mice

Ashish K. Rehni, Thakur Gurjeet Singh, Rohit Kalra, Nirmal Singh

Research output: Contribution to journalArticlepeer-review

27 Scopus citations

Abstract

The present study has been designed to pharmacologically expound the significance of inducible nitric oxide synthase in the pathophysiological progression of seizures using mouse models of chemically induced kindled epilepsy and status epilepticus induced spontaneous recurrent seizures. Pentylenetetrazole (40 mg kg-1) (PTZ) administration every second day for a period of 15 days was used to elicit kindled seizure activity in mice. Severity of kindled seizures was assessed in terms of a composite kindled seizure severity score (KSSS). Pilocarpine (100 mg kg-1) was injected every 20 min 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 induced the development of severe form of kindled seizures in mice. Further, pharmacological status epilepticus elicited a progressive evolution of spontaneous recurrent seizures in the animals. However, treatment of aminoguanidine, a relatively selective inhibitor of inducible nitric oxide synthase, markedly and dose dependently suppressed the development of both PTZ induced kindled seizures as well as pilocarpine induced spontaneous recurrent seizures. Therefore inducible nitric oxide synthase may be implicated in the development of seizures.

Original languageEnglish (US)
Pages (from-to)120-125
Number of pages6
JournalNitric Oxide - Biology and Chemistry
Volume21
Issue number2
DOIs
StatePublished - Sep 15 2009
Externally publishedYes

Keywords

  • Aminoguanidine
  • Inducible nitric oxide synthase
  • Seizures

ASJC Scopus subject areas

  • Biochemistry
  • Physiology
  • Clinical Biochemistry
  • Cancer Research

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