Treatment with carnosine reduces hypoxia-ischemia brain damage in a neonatal rat model.

Abstract

Perinatal hypoxia-ischemia brain damage (HIBD) is a major cause of mortality and morbidity in neonates, and there is currently no effective therapy for HIBD. Carnosine plays a neuroprotective role in adult brain damage. We have previously demonstrated that carnosine pretreatment protects against HIBD in a neonatal rat model. Therefore, we hypothesized that treatment with carnosine would also have neuroprotective effects. Hypoxia-ischemia was induced in rats on postnatal days 7-9 (P7-9). Carnosine was administered intraperitoneally at a dose of 250mg/kg at 0h, 24h, and 48h after hypoxia-ischemia was induced. The biochemical markers of oxidative stress and apoptosis were evaluated at 72h after hypoxia-ischemia was induced, Brain learning and memory function performance were observed using the Morris water maze test on postnatal days 28-33 (P28-33). Treatment with carnosine post-HIBD significantly reduced the concentration of 8-iso-prostaglandinF2alpha in brain tissue and decreased the number of terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) positive cells in the hippocampus CA1 region and cortex as well as the mitochondria caspase-3 protein expression. Furthermore, carnosine also improved the cognitive function of P28-33 rats, whose cognitive function decline was due to HIBD. These results demonstrate that carnosine treatment after HIBD can reduce the brain injury, improving brain function. Carnosine could be an attractive candidate for treating HIBD.

• Authors: Huizhen Zhang, Shang Guo, Linlin Zhang, Liting Jia, Zhan Zhang, Hongbao Duan, Jingbin Zhang, Jingyan Liu, Weidong Zhang
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 727 Pg. 174-80 (Mar 15 2014) ISSN: 1879-0712 [Electronic] Netherlands
• PMID: 24463179 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Elsevier B.V. All rights reserved.

Chemical References

• Biomarkers
• Neuroprotective Agents
• Carnosine

Topics

• Animals
• Animals, Newborn
• Apoptosis (drug effects)
• Behavior, Animal (drug effects)
• Biomarkers (metabolism)
• Brain (drug effects, metabolism, pathology)
• Carnosine (administration & dosage, pharmacology)
• Cognition (drug effects)
• Disease Models, Animal
• Hypoxia-Ischemia, Brain (metabolism, pathology, prevention & control, psychology)
• Injections, Intraperitoneal
• Maze Learning (drug effects)
• Memory (drug effects)
• Neuroprotective Agents (administration & dosage, pharmacology)
• Oxidative Stress (drug effects)
• Rats, Sprague-Dawley
• Time Factors