Combination of Citicoline and L-NAME Restores Neurological Functions, Reverts Biochemical Alterations and Reduces Neuronal Damage in Transient Focal Cerebral Ischemic Rats

Abstract

Objectives: To investigate the neuroprotective effect of combination of Citicoline (membrane stabilizer) and L-NAME (NOS inhibitor) in middle cerebral artery occluded/reperfused rats (MCAO/R). Methods: Citicoline (250 mg/kg b.w.) followed by L-NAME (3 mg/kg b.w.) was administered 30 minutes before (Pre) performing middle cerebral artery occlusion/reperfusion (MCAO/R) in Sprague Dawley rats. Parameters such as Glutamate, Aspartate, Nitrite/Nitrate, Sodium potassium ATPase (Na + K + ATPase) content, expression of TNF-α and IL-10, and histopathology was studied. Neurological scoring was also performed in the MCAO/R rats. Findings: Pre ischemic administration of citicoline and L-NAME has improved neurological deficit (p<0.001). Combination treatment has also ameliorated the glutamate level in MCAO/R rats (p<0.05). Combination of these drugs has also reduced the nitrate/nitrite content (p<0.001) and also sodium potassium ATPase (Na + K + ATPase) (p<0.001) significantly. Citicoline and L-NAME combination treatment has also down regulated the expression of TNF-α and up regulated the expression of IL-10 in middle cerebral artery occlusion/reperfusion rats. Citicoline and L-NAME combination was also observed to reduce the neuronal damage which is evident from the histopathology (H and E) of brain sections of MCAO/R rats. Novelty of the Study: Though Citicoline and L-NAME has been evaluated and proven for their neuroprotection separately, the effect of these two drugs when administered together as a combination has not been studied. This study is first of its kind to determine the neuroprotective effect of combination of citicoline and L-NAME. Conclusion/Application: Combination of citicoline and L-NAME has profoundly improved neuroprotection and ameliorated excitotoxicity when administered 30 minutes before ischemia.