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Neuroprotective actions of pterostilbene on hypoxic‐ischemic brain damage in neonatal rats through upregulation of heme oxygenase‐1
Author(s) -
Li Dan,
Song Tingting,
Yang Lin,
Wang Xueying,
Yang Changhong,
Jiang Yongsheng
Publication year - 2016
Publication title -
international journal of developmental neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.761
H-Index - 88
eISSN - 1873-474X
pISSN - 0736-5748
DOI - 10.1016/j.ijdevneu.2016.08.005
Subject(s) - neuroprotection , oxidative stress , heme oxygenase , brain damage , proinflammatory cytokine , pharmacology , pterostilbene , medicine , superoxide dismutase , reactive oxygen species , inflammation , tunel assay , anesthesia , chemistry , biochemistry , endocrinology , apoptosis , heme , resveratrol , enzyme
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.