Neuroprotective effect of carnosine and cyclosporine-A against inflammation, apoptosis, and oxidative brain damage after closed head injury in immature rats.
Traumatic brain injury in the pediatric population can have a great economic and emotional impact on both the child's family and society.



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.



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.



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.



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.
a Department of Pharmacology , King Saud University , Riyadh , Saudi Arabia.|Pharmacology Department, Faculty of Pharmacy, Al-Azhar University, Cairo, Egypt.
Nayira Ahmed Abdel
NA
Baky
a Department of Pharmacology , King Saud University , Riyadh , Saudi Arabia.
Laila
L
Fadda
a Department of Pharmacology , King Saud University , Riyadh , Saudi Arabia.
Nouf M
NM
Al-Rasheed
a Department of Pharmacology , King Saud University , Riyadh , Saudi Arabia.
Nawal M
NM
Al-Rasheed
b Biochemistry Department, Faculty of Science for Girls , King Abdulaziz University , Jeddah , Saudi Arabia.
Azza
A
Mohamed
a Department of Pharmacology , King Saud University , Riyadh , Saudi Arabia.
Hazar
H
Yacoub
D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000276:immunology; D015415:Biomarkers / Q000032:analysis; D001921:Brain / Q000187:drug effects / Q000254:growth & development / Q000276:immunology / Q000378:metabolism; D002336:Carnosine / Q000008:administration & dosage / Q000627:therapeutic use*; D016572:Cyclosporine / Q000008:administration & dosage / Q000627:therapeutic use*; D016207:Cytokines / Q000276:immunology; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D016489:Head Injuries, Closed / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008297:Male; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D018384:Oxidative Stress / Q000187:drug effects* / Q000276:immunology; D017208:Rats, Wistar
D015415:Biomarkers; D016207:Cytokines; D018696:Neuroprotective Agents; D016572:Cyclosporine; D002336:Carnosine
Calcium–adenosine triphosphatase; lipid peroxidation; oxidative damage; sFasL; traumatic brain injury