iridoids and Hypoxia-Ischemia--Brain

N-Methyl-D-aspartate receptor (NMDAR)-induced antioxidation is a significant cause of neuronal injury after ischemic stroke. In a previous work, we verified the neuroprotective roles of geniposide during tMCAO in vivo. However, it remains unknown whether geniposide ameliorates injury to hippocampal neurons during Ischemic Long Term Potentiation (iLTP) induction in vitro. After induction of cells oxygen-glucose deprivation or hydrogen peroxide, the protection of geniposide evaluated by MTT assay and electrophysiological tests. In this study, we suggested neuronal cell apoptosis was attenuated by geniposide. Furthermore, field excitatory postsynaptic potentials (fEPSCs) following postischemic LTP were assessed by electrophysiological tests. Finally, we determined that medium and high doses of geniposide attenuated oxidative stress insult and improved iLTP. Importantly, these effects were abolished by cotreatment with geniposide and the GluN2A antagonist NVP. In contrast, the GluN2B inhibitor ifenprodil failed to have an effect. In conclusion, we suggest for the first time that treatment with geniposide can attenuate postischemic LTP induction in a concentration-dependent manner. We infer that GluN2A-containing NMDARs are involved in the neuroprotection induced by geniposide treatment in ischemia.

Topics: Animals; Apoptosis; Excitatory Amino Acid Antagonists; Excitatory Postsynaptic Potentials; Hippocampus; Hydrogen Peroxide; Hypoxia-Ischemia, Brain; In Vitro Techniques; Infarction, Middle Cerebral Artery; Iridoids; Long-Term Potentiation; Neurons; Oxidants; PC12 Cells; Piperidines; Quinoxalines; Rats; Receptors, N-Methyl-D-Aspartate

Perinatal hypoxic-ischemia (HI) is a leading cause of acute mortality and neurologic complications in newborns. Geniposide, a natural product extracted from the herb Gardenia jasminoides, has been shown to possess neuroprotective effects in neurologic deficits. This study aims to investigate whether Geniposide has therapeutic potential to HI brain injury and the underlying mechanisms. C57/bl6 mice were subjected to HI insult on postnatal day 10. Geniposide (20 mg/kg b.w.) was administered intragastrically every day after HI insult for 7 successional days. Then mice at P18 were sacrificed and brain tissues were collected for further analysis. Geniposide treatment significantly inhibited cell apoptosis, reduced serum IgG leakage into brain tissue, attenuated astrogliosis and microgliosis, prevented loss of pericytes, loss of tight junction and adherens junction proteins. The PI3K/Akt signaling pathway, which related proteins were downregulated after HI insult, was activated by Geniposide treatment. Geniposide treatment after neonatal HI insult attenuated HI-induced cell apoptosis, IgG leakage, microgliosis, astrogliosis, pericytes loss and junction protein degradation. Geniposide could protect against HI-induced brain injury, which might be through the activation of PI3K/Akt signaling pathway.

Topics: Animals; Apoptosis; Astrocytes; Brain; Female; Hypoxia-Ischemia, Brain; Iridoids; Male; Mice; Microglia; Neuroprotective Agents; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins c-akt; Signal Transduction

This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/our-business/policies/article-withdrawal).\ \ This article has been retracted at the request of the Editor-in-Chief.\ \ Given the comments of Dr Elisabeth Bik regarding this article “… the Western blot bands in all 400+ papers are all very regularly spaced and have a smooth appearance in the shape of a dumbbell or tadpole, without any of the usual smudges or stains. All bands are placed on similar looking backgrounds, suggesting they were copy/pasted from other sources, or computer generated”, the journal requested the authors to provide the raw data. However, the authors were not able to fulfil this request and therefore the Editor-in-Chief decided to retract the article.

Topics: Animals; Apoptosis; Blotting, Western; Cell Proliferation; Cell Survival; Gene Knockdown Techniques; Glucose; Hypoxia-Ischemia, Brain; Iridoids; Oxygen; PC12 Cells; Phosphatidylinositol 3-Kinase; Proto-Oncogene Proteins c-akt; Rats; RNA, Long Noncoding; Signal Transduction; Up-Regulation; Wnt Signaling Pathway