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To investigate the therapeutic efficacy of Scutellarin (SCU) on neurite growth and neurological functional recovery in neonatal hypoxic-ischemic (HI) rats. Primary cortical neurons were cultured to detect the effect of SCU on cell viability of neurons under oxygen-glucose deprivation (OGD). Double immunofluorescence staining of Tuj1 and TUNEL then observed the neurite growth and cell apoptosis in vitro, and double immunofluorescence staining of NEUN and TUNEL was performed to examine the neuronal apoptosis and cell apoptosis in brain tissues after HI in vivo . Pharmacological efficacy of SCU was also evaluated in HI rats by neurobehavioral tests, triphenyl tetrazolium chloride staining, Hematoxylin and eosin staining and Nissl staining. Astrocytes and microglia expression in damaged brain tissues were detected by immunostaining of GFAP and Iba1. A quantitative real-time polymerase chain reaction and western blot were applied to investigate the genetic expression changes and the protein levels of autophagy-related proteins in the injured cortex and hippocampus after HI. We found that SCU administration preserved cell viability, promoted neurite outgrowth and suppressed apoptosis of neurons subjected to OGD both in vitro and in vivo. Meanwhile, 20 mg/kg SCU treatment improved neurological functions and decreased the expression of astrocytes and microglia in the cortex and hippocampus of HI rats. Additionally, SCU treatment depressed the elevated levels of autophagy-related proteins and the p75 neurotrophin receptor (p75NTR) in both cortex and hippocampus. This study demonstrated the potential therapeutic efficacy of SCU by enhancing neurogenesis and restoring long-term neurological dysfunctions, which might be associated with p75NTR depletion in HI rats.

Aims: In this study we aimed to explore the specific effect and mechanism of oxymatrine on neonatal rats hypoxic-ischemic brain damage., Materials and Methods: Hypoxia-ischemia damage model was built by ligaturing the left common carotid artery in 7-day-old rat. Rat pups in OMT group received intraperitoneal injection with oxymatrine (120 mg/kg). Oxygen glucose deprivation/reperfusion model was created in hippocampal neurons. Neurological behavioral, histopathological alteration, cell viability, intracellular Ca 2+ concentration, MMP and cell apoptosis were used in damage evaluation., Key Findings: The results shown that oxymatrine regulated brain damage and cell apoptosis by controlling NR2B-PI3K/Akt/GSK3β signaling pathway., Significance: Neonatal hypoxic-ischemic brain damage is a destructive injury that leading to death and detrimental neurological deficits. Oxymatrine is a natural alkaloid compound that can alleviate the ischemic cerebral infarction. In the study, 120 mg/kg oxymatrine decreased neuroethology damage and neuronal damage in the cerebral cortex and the hippocampus CA3. Moreover, 0.2, 1, 5 μg/ml oxymatrine improved cell survival, decreased cell apoptosis. The utilization of LY293004 (PI3K signaling pathway inhibitor) also supported that oxymatrine ameliorated neonatal hypoxic-ischemic brain damage and cell injury by controlling NR2B-PI3K/Akt/GSK3β signaling pathway., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflicts of interest., (Copyright © 2019. Published by Elsevier Inc.)

Neonatal hypoxic-ischemic brain damage (HIBD) is a leading cause of death and perpetual neurological dysfunction in neonates. Vanillin (Van), a natural phenolic compound with neuroprotective properties, exerts neuroprotection on a gerbil model of global ischemia by inhibiting oxidative damage. This study aimed to explore the potential neuroprotective roles of Van in neonatal rats suffering from hypoxic-ischemic (HI). An HI model of 7-day-old SD rats was induced by left carotid artery ligation followed by exposure to 8% oxygen (balanced with nitrogen) for 2.5 h at 37 °C. At 48 h after intraperitoneal injection with Van (20, 40, and 80 mg/kg) or saline, neurobehavioral function, cerebral infract volume, brain water content, and histomorphological changes were performed to evaluate brain injury. Transmission electron microscopy and immunoglobulin G (IgG) staining were conducted to evaluate the integrity of the blood-brain barrier (BBB). The levels of oxidative stress and tight junction proteins, as well as the activities of matrix metalloproteinases (MMPs), were also determined in the ipsilateral hemisphere. Results showed that Van post-treatment significantly ameliorated early neurobehavioral deficits, decreased infarct volume and brain edema, as well as attenuated histopathologic injury and IgG extravasation. Furthermore, Van markedly increased the activities of endogenous antioxidant enzymes and decreased malondialdehyde content. Meanwhile, the activation of MMP-2 and MMP-9 induced by HI was partially blocked by Van. Finally, Van obviously increased the expression of ZO-1, Occludin, and Claudin-5 compared with the HI group. Collectively, Van can provide neuroprotective effects against neonatal HIBD possibly by attenuating oxidative damage and preserving BBB integrity., (Copyright © 2019 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)