Pediatric Pharmacology and Therapeutics

Role of nitric oxide (NO) inhibition in cerebral ischemia/reperfusion (I/R) remains uncertain; this work aimed to explore the neuroprotective potential of N-Nitro-L-Arginine-Methylester (L-NAME) non-selective NO synthase (NOS) inhibitors. Th e study involved 30 adult male Wistar rats (150-250g), divided into three groups;10 rats in each: sham-operated group (control), I/R group: infused with 0.9% normal saline intraperitoneally prior to 30 minutes of left common carotid artery occlusion followed by 24-hours of reperfusion, third group (test group): infused with L-NAME (15 mg/kg per weight) intraperitoneally 15 minutes prior to the same I/R period. Neurobehavioral assessments were evaluated using six clinical tests. Proper anesthesia was induced. Western blotting was used to estimate Nuclear factor kappa B (NF-κB), Tumor necrosis factor-α (TNF-α) using ELISA and NO metabolites (nitrite and nitrate), were measured colorimetrically in both plasma and

aff ected cerebral hemisphere. Th e result shows that L-NAME group demonstrates a signifi cant improvement in neurological deficit (P <0.001) compared to both I/R and control groups. In I/R rats NF-κB was signifi cantly increased compared to the control group and L-NAME pretreatment resulted in a signifi cant decrease in NF-κB (P <0.001) compared to I/R group. Serum level of TNF-α and NO were signifi cantly increased in I/R group compared to the control group (P <0.001), while L-NAME administration resulted in a signifi cant decrease in serum TNF-α and NO (P <0.001) compared to the I/R group. In conclusions, L-NAME pretreatment for rats undergoing cerebral ischemia/reperfusion signifi cantly improve neurological deficit through it is anti-infl ammatory eff ect in a rat’s model of transient focal cerebral ischemia-reperfusion.