Pharmacological inhibition of inducible nitric oxide synthase attenuates the development of seizures in mice.
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.
Rehni
Ashish K
AK
Chitkara College of Pharmacy, Chandigarh-Patiala National Highway, Rajpura 140401, Patiala, Punjab, India. ashishkrehni@gmail.com
Singh
Thakur Gurjeet
TG
Kalra
Rohit
R
Singh
Nirmal
N
D000704:Analysis of Variance; D000818:Animals; D003292:Convulsants; D006146:Guanidines / Q000494:pharmacology*; D008297:Male; D051379:Mice; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors* / Q000378:metabolism; D010433:Pentylenetetrazole; D010862:Pilocarpine; D012640:Seizures / Q000139:chemically induced / Q000201:enzymology* / Q000517:prevention & control; D013226:Status Epilepticus / Q000139:chemically induced / Q000201:enzymology / Q000517:prevention & control
D003292:Convulsants; D006146:Guanidines; D010862:Pilocarpine; D052247:Nitric Oxide Synthase Type II; C004479:pimagedine; D010433:Pentylenetetrazole