scholarly journals Galectin-3 modulates microglia inflammation in vitro but not neonatal brain injury in vivo under inflammatory conditions

2021 ◽  
Author(s):  
Karin Sävman ◽  
Wei Wang ◽  
Ali Hoseinpoor Rafati ◽  
Pernilla Svedin ◽  
Syam Nair ◽  
...  
Keyword(s):  
Brain Injury ◽  
Neonatal Brain ◽  
Neonatal Brain Injury ◽  
Inflammatory Conditions ◽  
Galectin 3

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 Programmed Necrosis: A Prominent Mechanism of Cell Death following Neonatal Brain Injury

2012 ◽  
Vol 2012 ◽  
pp. 1-12 ◽  
Author(s):  
Raul Chavez-Valdez ◽  
Lee J. Martin ◽  
Frances J. Northington
Keyword(s):  
Cell Death ◽  
Brain Injury ◽  
Significant Proportion ◽  
Developing Brain ◽  
Neonatal Brain ◽  
Programmed Necrosis ◽  
Interacting Protein ◽  
Neonatal Brain Injury ◽  
Regulated Necrosis

Despite the introduction of therapeutic hypothermia, neonatal hypoxic ischemic (HI) brain injury remains a common cause of developmental disability. Development of rational adjuvant therapies to hypothermia requires understanding of the pathways of cell death and survival modulated by HI. The conceptualization of the apoptosis-necrosis “continuum” in neonatal brain injury predicts mechanistic interactions between cell death and hydrid forms of cell death such as programmed or regulated necrosis. Many of the components of the signaling pathway regulating programmed necrosis have been studied previously in models of neonatal HI. In some of these investigations, they participate as part of the apoptotic pathways demonstrating clear overlap of programmed death pathways. Receptor interacting protein (RIP)-1 is at the crossroads between types of cellular death and survival and RIP-1 kinase activity triggers formation of the necrosome (in complex with RIP-3) leading to programmed necrosis. Neuroprotection afforded by the blockade of RIP-1 kinase following neonatal HI suggests a role for programmed necrosis in the HI injury to the developing brain. Here, we briefly review the state of the knowledge about the mechanisms behind programmed necrosis in neonatal brain injury recognizing that a significant proportion of these data derive from experiments in cultured cell and some from in vivo adult animal models. There are still more questions than answers, yet the fascinating new perspectives provided by the understanding of programmed necrosis in the developing brain may lay the foundation for new therapies for neonatal HI.

Hyperoxia and neonatal brain injury

2005 ◽  
Vol 36 (02) ◽  
Author(s):  
U Felderhoff-Mueser ◽  
AM Kaindl ◽  
C Bührer ◽  
H Ikonomidou
Keyword(s):  
Brain Injury ◽  
Neonatal Brain ◽  
Neonatal Brain Injury

HISTOLOGICAL INFLAMMATORY RESPONSES IN THE PLACENTA AND EARLY NEONATAL BRAIN INJURY

2006 ◽  
Vol preprint (2008) ◽  
pp. 1
Author(s):  
Vincenzo Zanardo ◽  
Stefania Vedovato ◽  
Agnese Suppiej ◽  
Daniele Trevisanuto ◽  
Mauro Migliore ◽  
...  
Keyword(s):  
Brain Injury ◽  
Inflammatory Responses ◽  
Neonatal Brain ◽  
Neonatal Brain Injury

scholarly journals TRAF3 mediates neuronal apoptosis in early brain injury following subarachnoid hemorrhage via targeting TAK1-dependent MAPKs and NF-κB pathways

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Yan Zhou ◽  
Tao Tao ◽  
Guangjie Liu ◽  
Xuan Gao ◽  
Yongyue Gao ◽  
...  
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Brain Injury ◽  
Therapeutic Target ◽  
Cortical Neurons ◽  
Neuronal Apoptosis ◽  
Early Brain Injury ◽  
Neurological Deficits ◽  
Human Brain Tissue

AbstractNeuronal apoptosis has an important role in early brain injury (EBI) following subarachnoid hemorrhage (SAH). TRAF3 was reported as a promising therapeutic target for stroke management, which covered several neuronal apoptosis signaling cascades. Hence, the present study is aimed to determine whether downregulation of TRAF3 could be neuroprotective in SAH-induced EBI. An in vivo SAH model in mice was established by endovascular perforation. Meanwhile, primary cultured cortical neurons of mice treated with oxygen hemoglobin were applied to mimic SAH in vitro. Our results demonstrated that TRAF3 protein expression increased and expressed in neurons both in vivo and in vitro SAH models. TRAF3 siRNA reversed neuronal loss and improved neurological deficits in SAH mice, and reduced cell death in SAH primary neurons. Mechanistically, we found that TRAF3 directly binds to TAK1 and potentiates phosphorylation and activation of TAK1, which further enhances the activation of NF-κB and MAPKs pathways to induce neuronal apoptosis. Importantly, TRAF3 expression was elevated following SAH in human brain tissue and was mainly expressed in neurons. Taken together, our study demonstrates that TRAF3 is an upstream regulator of MAPKs and NF-κB pathways in SAH-induced EBI via its interaction with and activation of TAK1. Furthermore, the TRAF3 may serve as a novel therapeutic target in SAH-induced EBI.

scholarly journals Macropinocytosis requires Gal-3 in a subset of patient-derived glioblastoma stem cells

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Laetitia Seguin ◽  
Soline Odouard ◽  
Francesca Corlazzoli ◽  
Sarah Al Haddad ◽  
Laurine Moindrot ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cell Survival ◽  
Small Gtpases ◽  
Molecular Signature ◽  
Carbohydrate Binding ◽  
Pancreatic Cancers ◽  
Galectin 3 ◽  
Pharmacologic Inhibition

AbstractRecently, we involved the carbohydrate-binding protein Galectin-3 (Gal-3) as a druggable target for KRAS-mutant-addicted lung and pancreatic cancers. Here, using glioblastoma patient-derived stem cells (GSCs), we identify and characterize a subset of Gal-3high glioblastoma (GBM) tumors mainly within the mesenchymal subtype that are addicted to Gal-3-mediated macropinocytosis. Using both genetic and pharmacologic inhibition of Gal-3, we showed a significant decrease of GSC macropinocytosis activity, cell survival and invasion, in vitro and in vivo. Mechanistically, we demonstrate that Gal-3 binds to RAB10, a member of the RAS superfamily of small GTPases, and β1 integrin, which are both required for macropinocytosis activity and cell survival. Finally, by defining a Gal-3/macropinocytosis molecular signature, we could predict sensitivity to this dependency pathway and provide proof-of-principle for innovative therapeutic strategies to exploit this Achilles’ heel for a significant and unique subset of GBM patients.

Drug delivery platforms for neonatal brain injury

2021 ◽  
Author(s):  
Rukhmani Narayanamurthy ◽  
Jung-Lynn Jonathan Yang ◽  
Jerome Y. Yager ◽  
Larry D. Unsworth
Keyword(s):  
Drug Delivery ◽  
Brain Injury ◽  
Neonatal Brain ◽  
Neonatal Brain Injury
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