The effects of riluzole on neurological, brain biochemical, and histological changes in early and late term of sepsis in rats.
OBJECTIVE
One of the underlying mechanisms of sepsis is thought to be the oxidative damage due to the generation of free radicals. Glutamate, the major excitatory amino acid in the brain, is known to play an important role in blood brain barrier (BBB) permeability, brain edema, and oxidative damage in pathological conditions. Riluzole, a glutamate release inhibitor, has been shown to have neuroprotective effects in several animal models. The aim of our study was to investigate the putative protective effect of riluzole against sepsis-induced brain injury.


METHODS
Sepsis was induced by cecal ligation and puncture in Wistar albino rats. Sham operated (control) and sepsis groups received either saline or riluzole (6 mg/kg, s.c.) 30 min after the surgical procedure, and every 12 h as continuing treatment. The effect of riluzole on the survival rate, weight loss, fever, leukocyte count, brain edema, BBB permeability, oxidative damage, and histological observations were evaluated for early (6 h) and late (48 h) phase of sepsis.


RESULTS
Riluzole, when administered 6 mg/kg s.c., diminishes the sepsis-induced augmentation in weight loss, body temperature, brain edema, increase in BBB permeability, oxidative damage, and brain injury that is observed histologically. Besides increasing the survival rate in sepsis, it has also improved neurological examination scores and the prognosis of the disease.


CONCLUSIONS
According to the results of this study, riluzole appears to have a protective effect for sepsis-induced encephalopathy.
Toklu
Hale Z
HZ
Department of Pharmacology, Marmara University School of Pharmacy, Istanbul, Turkey. haletoklu@yahoo.com
Uysal
Meral Keyer
MK
Kabasakal
Levent
L
Sirvanci
Serap
S
Ercan
Feriha
F
Kaya
Mehmet
M
D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000502:physiology*; D001831:Body Temperature / Q000187:drug effects; D001921:Brain / Q000166:cytology / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D001929:Brain Edema / Q000139:chemically induced; D001930:Brain Injuries / Q000139:chemically induced*; D002463:Cell Membrane Permeability / Q000187:drug effects / Q000502:physiology; D005260:Female; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D018696:Neuroprotective Agents / Q000494:pharmacology; D010146:Pain / Q000503:physiopathology; D010147:Pain Measurement / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D019782:Riluzole / Q000494:pharmacology*; D018805:Sepsis / Q000378:metabolism* / Q000473:pathology
D018696:Neuroprotective Agents; D019782:Riluzole