title: Neuroprotective actions of pterostilbene on hypoxic-ischemic brain damage in neonatal rats through upregulation of heme oxygenase-1.
abstract: Neonatal hypoxic-ischemic (HI) brain damage causes acute mortality and morbidity in newborns and long-term neurological disorders in the survivors. Pterostilbene (PTE) is a natural compound possessing various biological and pharmacological activities. In the present study, we aimed to investigate the effect of PTE on neonatal HI brain damagein P7 rat model and to explore the possible mechanisms. Neonatal HI brain damage was induced in rat pups (P7). Prior to the induction of HI injury, PTE was injected with or without zinc protoporphyrin IX (ZnPP), an inhibitor of heme oxygenase-1 (HO-1). ZnPP was used to test whether abnormal changes of HO-1 expression were involved in the effect of PTE. The results showed that PTE exhibited excellent neuroprotective effects against neonatal HI brain injury, as evidenced by the decrease of brain infarct volume, brain edema, neurological score, and improvement in motor coordination motor deficit and working memory deficit. PTE pretreatment decreased the expression of several proinflammatory cytokines, including TNFα, IL-1β, IL-6, and key transcription factor p65 NF-κB, and reduced the number of TUNEL-stained neurons, indicating the inhibition of inflammation and programmed cell death. Moreover, PTE pretreatment decreased thiobarbituric acid reactive substances content, increased superoxide dismutase activity and decreased reactive oxygen species level, indicating that PTE played an important antioxidant role. Furthermore, ZnPP was able to inhibit PTE-induced suppression of oxidative stress, programmed cell death, inflammation and brain damage. In conclusion, PTE pretreatment prevented HI-induced brain injury in newborns through HO-1-mediated reduction of oxidative stress, programmed cell death, and inflammation, and final improvement of histological and functional injury. Overall, the data that obtained in rat model provide novel insights into the pathogenesis of neonatal HI brain injury and may be translational to human clinical intervention for HI-associated brain injury in newborns.
authors: Department of Pediatrics, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, Shaanxi Province, China.
authors: Dan
authors: D
authors: Li
authors: Department of Pediatrics, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, Shaanxi Province, China.
authors: Tingting
authors: T
authors: Song
authors: Department of Pediatrics, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, Shaanxi Province, China. Electronic address: lin_yang2002@126.com.
authors: Lin
authors: L
authors: Yang
authors: Department of Pediatrics, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, Shaanxi Province, China.
authors: Xueying
authors: X
authors: Wang
authors: Department of Pediatrics, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, Shaanxi Province, China.
authors: Changhong
authors: C
authors: Yang
authors: Department of Pediatrics, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, Shaanxi Province, China.
authors: Yongsheng
authors: Y
authors: Jiang
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D001929:Brain Edema / Q000209:etiology / Q000517:prevention & control; D001930:Brain Injuries / Q000209:etiology / Q000517:prevention & control*; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D020233:Gait Disorders, Neurologic / Q000209:etiology / Q000517:prevention & control; D006419:Heme Oxygenase (Decyclizing) / Q000235:genetics / Q000378:metabolism*; D020925:Hypoxia-Ischemia, Brain / Q000150:complications*; D008297:Male; D008569:Memory Disorders / Q000209:etiology / Q000517:prevention & control; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D011524:Protoporphyrins / Q000494:pharmacology; D011596:Psychomotor Disorders / Q000209:etiology / Q000517:prevention & control; D051381:Rats; D013267:Stilbenes / Q000494:pharmacology* / Q000627:therapeutic use*; D015854:Up-Regulation / Q000187:drug effects*
chemical_list: D016207:Cytokines; D004791:Enzyme Inhibitors; D018696:Neuroprotective Agents; D011524:Protoporphyrins; D013267:Stilbenes; C017803:zinc protoporphyrin; C107773:pterostilbene; D006419:Heme Oxygenase (Decyclizing); C491523:Hmox1 protein, rat
keywords: Brain damage; HI; Heme oxygenase-1; Neonatal rat; Pterostilbene