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.

Conclusion

According to the results of this study, riluzole appears to have a protective effect for sepsis-induced encephalopathy.

Key Words: riluzole, glutamate, sepsis, encephalopathy, blood brain barrier, antioxidant, neuroprotective, MDA, glutathione