title: Carnosine pretreatment protects against hypoxia-ischemia brain damage in the neonatal rat model.
abstract: Perinatal hypoxia-ischemia brain injury is a major cause of mortality and morbidity in neonates and lacks an effective treatment thus far. Carnosine has been demonstrated to play a neuroprotective role in the adult brain injuries. However, there is no information available concerning its neuroprotective role in the immature brains after hypoxia-ischemia insults. Therefore, we investigated whether carnosine could also confer neuroprotective effects in a neonatal rat hypoxia-ischemia model. Hypoxia-ischemia was induced in rats on postnatal day 7 (P7). Carnosine (250 mg/kg) was administered intraperitoneally, 30 min prior to hypoxia-ischemia induction. Morphological brain injury and biochemical markers of apoptosis and oxidative stress were evaluated 24 h after hypoxia-ischemia induction. Cognitive performance was evaluated by the Morris Water Maze test on P28-P33. We found that pretreatment with carnosine significantly reduced the infarct volume and the number of terminal-deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL)-positive cells in the hypoxia-ischemia brain. Carnosine also inhibited mRNA expression of apoptosis-inducing factor(AIF) and caspase-3, which was accompanied by an increase in superoxide dismutase(SOD)activity and a decrease in the malondialdehyde(MDA)level in carnosine-treated rats. Furthermore, carnosine also improved the spatial learning and memory abilities of rats declined due to hypoxia-ischemia. These results demonstrate that carnosine can protect rats against hypoxia-ischemia-induced brain damage by antioxidation.
authors.affiliation: Department of Clinical Laboratory, Third Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China.
authors.forename: Xiangmin
authors.initials: X
authors.lastname: Zhang
authors.forename: Lili
authors.initials: L
authors.lastname: Song
authors.forename: Xiuyong
authors.initials: X
authors.lastname: Cheng
authors.forename: Yi
authors.initials: Y
authors.lastname: Yang
authors.forename: Bin
authors.initials: B
authors.lastname: Luan
authors.forename: Liting
authors.initials: L
authors.lastname: Jia
authors.forename: Falin
authors.initials: F
authors.lastname: Xu
authors.forename: Zhan
authors.initials: Z
authors.lastname: Zhang
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D000975:Antioxidants / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D051033:Apoptosis Inducing Factor / Q000235:genetics; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D020520:Brain Infarction / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology; D002336:Carnosine / Q000494:pharmacology* / Q000627:therapeutic use; D053148:Caspase 3 / Q000235:genetics; D004195:Disease Models, Animal; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D020925:Hypoxia-Ischemia, Brain / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology / Q000517:prevention & control*; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008568:Memory / Q000187:drug effects; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D018384:Oxidative Stress / Q000187:drug effects; D011247:Pregnancy; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013037:Spatial Behavior / Q000187:drug effects / Q000502:physiology; D016019:Survival Analysis; D013997:Time Factors
chemical_list: D000975:Antioxidants; D051033:Apoptosis Inducing Factor; D018696:Neuroprotective Agents; D012333:RNA, Messenger; D002336:Carnosine; D053148:Caspase 3