Neuroprotective effect of carnosine and cyclosporine-A against inflammation, apoptosis, and oxidative brain damage after closed head injury in immature rats.

ABSTRACT

CONTEXT Traumatic brain injury in the pediatric population can have a great economic and emotional impact on both the child's family and society. OBJECTIVE: The present study aimed to compare the effects of carnosine (CAR) and/or cyclosporine A (CyA) on oxidative brain damage after closed head injury (CHI) in immature rats. MATERIALS AND METHODS: Thirty-day-old rat pups were divided into five groups non-traumatic control group, trauma group underwent CHI, trauma group injected with CAR (200 mg/kg, i.p.) following CHI for 7 d, trauma group injected with CyA (20 mg/kg, i.p.) given 15 min and 24 h after CHI, and trauma group treated with CAR and CyA. At the end of the treatment, rats were sacrificed; blood and brains were collected for assessing different biochemical parameters. RESULTS: Trauma significantly increased brain level of malondialdehyde, nitric oxide, glucose, calcium, inflammatory mediators. Brain DNA damage was confirmed by comet assay and the significant increase in brain caspase-3 activity. Moreover, the serum level of Fas ligand in traumatized animals was significantly elevated. Concomitant decrease in brain-reduced glutathione (GSH) and calcium-adenosine triphosphatase activity was observed in the traumatized-untreated group. Treatment of traumatized animals with CAR and/or CyA ameliorated all the biochemical changes induced by CHI with marked protective effect in the combination group. DISCUSSION AND CONCLUSION: CAR and CyA exerted a synergistic neuroprotective effect against CHI through blocking the induction of lipid peroxidation, reducing inflammatory, and oxidative stress biomarkers, preserving brain GSH content, and reducing the alterations in brain apoptotic biomarkers in traumatized animals.