scholarly journals Necrostatin Decreases Oxidative Damage, Inflammation, and Injury after Neonatal HI

2010 ◽  
Vol 31 (1) ◽  
pp. 178-189 ◽  
Author(s):  
Frances J Northington ◽  
Raul Chavez-Valdez ◽  
Ernest M Graham ◽  
Sheila Razdan ◽  
Estelle B Gauda ◽  
...  
Keyword(s):  
Cell Death ◽  
Brain Injury ◽  
Oxidative Damage ◽  
Apoptotic Cell ◽  
Death Domain ◽  
Neonatal Brain ◽  
Neonatal Brain Injury ◽  
Markers Of Inflammation ◽  
Gene And Protein Expression ◽  
Hypoxia Ischemia

Necrostatin-1 inhibits receptor-interacting protein (RIP)-1 kinase and programmed necrosis and is neuroprotective in adult rodent models. Owing to the prominence of necrosis and continuum cell death in neonatal hypoxia–ischemia (HI), we tested whether necrostatin was neuroprotective in the developing brain. Postnatal day (P)7 mice were exposed to HI and injected intracerebroventricularly with 0.1 μL of 80 μmol necrostatin, Nec-1, 5-(1H-Indol-3-ylmethyl)-(2-thio-3-methyl) hydantoin, or vehicle. Necrostatin significantly decreased injury in the forebrain and thalamus at P11 and P28. There was specific neuroprotection in necrostatin-treated males. Necrostatin treatment decreased necrotic cell death and increased apoptotic cell death. Hypoxia–ischemia enforced RIP1–RIP3 complex formation and inhibited RIP3–FADD (Fas-associated protein with death domain) interaction, and these effects were blocked by necrostatin. Necrostatin also decreased HI-induced oxidative damage to proteins and attenuated markers of inflammation coincidental with decreased nuclear factor-κB and caspase 1 activation, and FLIP ((Fas-associated death-domain-like IL-1β-converting enzyme)-inhibitory protein) gene and protein expression. In this model of severe neonatal brain injury, we find that cellular necrosis can be managed therapeutically by a single dose of necrostatin, administered after HI, possibly by interrupting RIP1–RIP3-driven oxidative injury and inflammation. The effects of necrostatin treatment after HI reflect the importance of necrosis in the delayed phases of neonatal brain injury and represent a new direction for therapy of neonatal HI.

Long non-coding RNA Snhg3 protects against hypoxia/ischemia-induced neonatal brain injury

2020 ◽  
Vol 112 ◽  
pp. 104343 ◽  
Author(s):  
Qing Yang ◽  
Ming-Fu Wu ◽  
Li-Hua Zhu ◽  
Li-Xing Qiao ◽  
Rui-Bin Zhao ◽  
...  
Keyword(s):  
Brain Injury ◽  
Neonatal Brain ◽  
Neonatal Brain Injury ◽  
Non Coding Rna ◽  
Hypoxia Ischemia ◽  
Long Non Coding Rna

GAS5 silencing protects against hypoxia/ischemia-induced neonatal brain injury

2018 ◽  
Vol 497 (1) ◽  
pp. 285-291 ◽  
Author(s):  
Rui-bin Zhao ◽  
Li-hua Zhu ◽  
Jia-Ping Shu ◽  
Li-Xing Qiao ◽  
Zheng-Kun Xia
Keyword(s):  
Brain Injury ◽  
Neonatal Brain ◽  
Neonatal Brain Injury ◽  
Hypoxia Ischemia

scholarly journals Alteration in Downstream Hypoxia Gene Signaling in Neonatal Glutathione Peroxidase Overexpressing Mouse Brain after Hypoxia-Ischemia

2015 ◽  
Vol 37 (4-5) ◽  
pp. 398-406 ◽  
Author(s):  
R. Ann Sheldon ◽  
Raha Sadjadi ◽  
Matthew Lam ◽  
Russell Fitzgerald ◽  
Donna M. Ferriero
Keyword(s):  
Cell Death ◽  
Brain Injury ◽  
Glutathione Peroxidase ◽  
Apoptotic Cell ◽  
Hypoxia Inducible Factor ◽  
Artery Ligation ◽  
Epo Receptor ◽  
Carotid Artery Ligation ◽  
Mouse Cortex ◽  
Hypoxia Ischemia

We have previously shown that glutathione peroxidase (GPx) overexpressing mice (hGPx-tg) have reduced brain injury after neonatal hypoxia-ischemia (HI) as a consequence of reduced hydrogen peroxide accumulation. However, this protection is reversed with hypoxia preconditioning, raising the question of the roles of the genes regulated by hypoxia-inducible factor-1α (HIF-1α) and their transcription products, such as erythropoietin (EPO), in both the initial protection and subsequent reversal of protection. hGPx-tg and their wild-type (WT) littermates underwent the Vannucci procedure of HI brain injury at postnatal day 9 - left carotid artery ligation followed by exposure to 10% oxygen for 50 min. Brain cortices and hippocampi were subsequently collected 0.5, 4 and 24 h later for the determination of protein expression by Western blot for GPx, HIF-1α, HIF-2α, EPO, EPO receptor, ERK1/2, phospho-ERK1/2, spectrin 145/150 (as a marker of calpain-specific necrotic cell death), and spectrin 120 (as a marker of apoptotic cell death mediated via caspase-3). As expected, the GPx overexpressing mouse cortex had approximately 3 times the GPx expression as WT naïve. Also, GPx expression remained higher in the GPx overexpressing brain than WT at all time points after HI (0.5, 4, 24 h). HIF-1α was not significantly changed in hGPx-tg as a consequence of HI but decreased in the WT cortex 4 h after HI. HIF-2α decreased in the WT hippocampus after HI. EPO was higher in the GPx overexpressing cortex and hippocampus 30 min after HI compared to WT, but the EPO receptor was unchanged by HI. ERK1/2 phosphorylation increased in the hippocampus at 4 h after HI and in the cortex at 24 h after HI in both WT and hGPx-tg. Spectrin 145/150 was increased in the WT cortex at 4 and 24 h after HI, and spectrin 120 increased 24 h after HI, perhaps reflecting greater injury in the WT brain, especially at 24 h when brain injury is more evident. The effect of GPx overexpression does not appear to upregulate the HIF pathway, yet EPO was upregulated, perhaps via ERK. This might explain, in part, why cell death takes a necrotic or apoptotic path. This may also be an explanation for why the GPx overexpressing brain cannot be preconditioned. This information may prove valuable in the development of therapies for neonatal HI brain injury.

scholarly journals Resveratrol post-treatment protects against neonatal brain injury after hypoxia-ischemia

Oncotarget ◽  
2016 ◽  
Vol 7 (48) ◽  
pp. 79247-79261 ◽  
Author(s):  
Shulin Pan ◽  
Songlin Li ◽  
Yingying Hu ◽  
Hao Zhang ◽  
Yanlong Liu ◽  
...  
Keyword(s):  
Brain Injury ◽  
Post Treatment ◽  
Neonatal Brain ◽  
Neonatal Brain Injury ◽  
Hypoxia Ischemia

scholarly journals Hypoxic Preconditioning Suppresses Glial Activation and Neuroinflammation in Neonatal Brain Insults

2015 ◽  
Vol 2015 ◽  
pp. 1-11 ◽  
Author(s):  
Chien-Yi Chen ◽  
Wei-Zen Sun ◽  
Kai-Hsiang Kang ◽  
Hung-Chieh Chou ◽  
Po-Nien Tsao ◽  
...  
Keyword(s):  
Brain Injury ◽  
Inflammatory Responses ◽  
Hypoxic Preconditioning ◽  
Glial Activation ◽  
Neonatal Brain ◽  
Mixed Glial Culture ◽  
Neonatal Brain Injury ◽  
Promising Therapeutic Approach ◽  
Hypoxia Ischemia

Perinatal insults and subsequent neuroinflammation are the major mechanisms of neonatal brain injury, but there have been only scarce reports on the associations between hypoxic preconditioning and glial activation. Here we use neonatal hypoxia-ischemia brain injury model in 7-day-old rats andin vitrohypoxia model with primary mixed glial culture and the BV-2 microglial cell line to assess the effects of hypoxia and hypoxic preconditioning on glial activation. Hypoxia-ischemia brain insult induced significant brain weight reduction, profound cell loss, and reactive gliosis in the damaged hemisphere. Hypoxic preconditioning significantly attenuated glial activation and resulted in robust neuroprotection. As early as 2 h after the hypoxia-ischemia insult, proinflammatory gene upregulation was suppressed in the hypoxic preconditioning group.In vitroexperiments showed that exposure to 0.5% oxygen for 4 h induced a glial inflammatory response. Exposure to brief hypoxia (0.5 h) 24 h before the hypoxic insult significantly ameliorated this response. In conclusion, hypoxic preconditioning confers strong neuroprotection, possibly through suppression of glial activation and subsequent inflammatory responses after hypoxia-ischemia insults in neonatal rats. This might therefore be a promising therapeutic approach for rescuing neonatal brain injury.

scholarly journals Osteopontin Reduced Hypoxia–Ischemia Neonatal Brain Injury by Suppression of Apoptosis in a Rat Pup Model

Stroke ◽  
2011 ◽  
Vol 42 (3) ◽  
pp. 764-769 ◽  
Author(s):  
Wanqiu Chen ◽  
Qingyi Ma ◽  
Hidenori Suzuki ◽  
Richard Hartman ◽  
Jiping Tang ◽  
...  
Keyword(s):  
Brain Injury ◽  
Neonatal Brain ◽  
Neonatal Brain Injury ◽  
Hypoxia Ischemia ◽  
Rat Pup
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