Treatment with carnosine reduces hypoxia-ischemia brain damage in a neonatal rat model.
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.
Department of Clinical Laboratory, The Third Affiliated Hospital of Zhengzhou University, Kangfuqian Street 7, Zhenzhou 450052, China.
Huizhen
H
Zhang
Department of Orthopaedics, Shanghai Sixth People׳s Affiliated Hospital of Shanghai JiaoTong University, Shanghai 200233, China.
Shang
S
Guo
Department of Clinical Laboratory, The Third Affiliated Hospital of Zhengzhou University, Kangfuqian Street 7, Zhenzhou 450052, China.
Linlin
L
Zhang
Department of Clinical Laboratory, The Third Affiliated Hospital of Zhengzhou University, Kangfuqian Street 7, Zhenzhou 450052, China.
Liting
L
Jia
Department of Clinical Laboratory, The Third Affiliated Hospital of Zhengzhou University, Kangfuqian Street 7, Zhenzhou 450052, China. Electronic address: zhangzhan27@gmail.com.
Zhan
Z
Zhang
Department of Pediatrics, Zhengzhou Central Affiliated Hospital of Zhengzhou University, Zhenzhou 450007, China.
Hongbao
H
Duan
Department of Pediatrics, Zhengzhou Central Affiliated Hospital of Zhengzhou University, Zhenzhou 450007, China.
Jingbin
J
Zhang
Department of Pediatrics, Zhengzhou Central Affiliated Hospital of Zhengzhou University, Zhenzhou 450007, China.
Jingyan
J
Liu
Department of Clinical Laboratory, The Third Affiliated Hospital of Zhengzhou University, Kangfuqian Street 7, Zhenzhou 450052, China.
Weidong
W
Zhang
D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000187:drug effects; D001522:Behavior, Animal / Q000187:drug effects; D015415:Biomarkers / Q000378:metabolism; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D002336:Carnosine / Q000008:administration & dosage / Q000494:pharmacology*; D003071:Cognition / Q000187:drug effects; D004195:Disease Models, Animal; D020925:Hypoxia-Ischemia, Brain / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control* / Q000523:psychology; D007274:Injections, Intraperitoneal; D018782:Maze Learning / Q000187:drug effects; D008568:Memory / Q000187:drug effects; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D015415:Biomarkers; D018696:Neuroprotective Agents; D002336:Carnosine
Allopurinol (PubChem CID: 2094); Carnosine; Carnosine (PubChem CID: 439224); Diethyl ether (PubChem CID: 3283); Hypoxia-ischemia; Magnesium sulfate (PubChem CID: 24083); Neonatal rat; Simvastatin (PubChem CID: 54454); Thioperamide (PubChem CID: 3035905); Treatment; α-Fluoromethylhistidine (PubChem CID: 107653)