ArticleCerebral cortex (New York, N.Y. : 1991)2013
Plasminogen activator inhibitor-1 mitigates brain injury in a rat model of infection-sensitized neonatal hypoxia-ischemia.
Article in Cerebral cortex (New York, N.Y. : 1991), 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers, 1 of them a synthesis that pooled it.
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Who cites it
26 citing papers in PubMed, 1 synthesis or guideline pooled it, 37 citations in OpenAlex.
- Neurological Outcome Following Newborn Encephalopathy With and Without Perinatal Infection: A Systematic Review.Frontiers in pediatrics · 2021Pooled it
- Hypothermia is not therapeutic in a neonatal piglet model of inflammation-sensitized hypoxia-ischemia.Pediatric research · 2022Trial
- No neuroprotective effect of therapeutic hypothermia following lipopolysaccharide-sensitized hypoxia-ischemia: a newborn piglet study.Frontiers in pediatrics · 2023Article
- Azithromycin reduces inflammation-amplified hypoxic-ischemic brain injury in neonatal rats.Pediatric research · 2022Article
- Creatine transporter deficiency impairs stress adaptation and brain energetics homeostasis.JCI insight · 2021Article
- Circulating tight-junction proteins are potential biomarkers for blood-brain barrier function in a model of neonatal hypoxic/ischemic brain injury.Fluids and barriers of the CNS · 2021Article
- Current Therapies for Neonatal Hypoxic-Ischaemic and Infection-Sensitised Hypoxic-Ischaemic Brain Damage.Frontiers in synaptic neuroscience · 2021Review
- Brain-targeted hypoxia-inducible factor stabilization reduces neonatal hypoxic-ischemic brain injury.Neurobiology of disease · 2021Article
- Monocytic Infiltrates Contribute to Autistic-like Behaviors in a Two-Hit Model of Neurodevelopmental Defects.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2020Article
- Fate mapping via CCR2-CreER mice reveals monocyte-to-microglia transition in development and neonatal stroke.Science advances · 2020Article
- The myth of the immature barrier systems in the developing brain: role in perinatal brain injury.The Journal of physiology · 2018Review
- Hypoxia-Preconditioned Human Umbilical Vein Endothelial Cells Protect Against Neurovascular Damage After Hypoxic Ischemia in Neonatal Brain.Molecular neurobiology · 2018Article
- Positive and negative conditioning in the neonatal brain.Conditioning medicine · 2018Article
- Neonatal Hypoxia Ischaemia: Mechanisms, Models, and Therapeutic Challenges.Frontiers in cellular neuroscience · 2017Review
- Protein kinase C-dependent growth-associated protein 43 phosphorylation regulates gephyrin aggregation at developing GABAergic synapses.Molecular and cellular biology · 2015Article
- Anti-tissue plasminogen activator (tPA) as an effective therapy of neonatal hypoxia-ischemia with and without inflammation.CNS neuroscience & therapeutics · 2015Review
- The role of inflammation in perinatal brain injury.Nature reviews. Neurology · 2015Review
- Blood-brain barrier dysfunction in disorders of the developing brain.Frontiers in neuroscience · 2015Review
- Blocking lymphocyte trafficking with FTY720 prevents inflammation-sensitized hypoxic-ischemic brain injury in newborns.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2014Article
- PreImplantation factor promotes neuroprotection by targeting microRNA let-7.Proceedings of the National Academy of Sciences of the United States of America · 2014Article
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
Intrauterine infection exacerbates neonatal hypoxic-ischemic (HI) brain injury and impairs the development of cerebral cortex. Here we used low-dose lipopolysaccharide (LPS) pre-exposure followed by unilateral cerebral HI insult in 7-day-old rats to study the pathogenic mechanisms. We found that LPS pre-exposure blocked the HI-induced proteolytic activity of tissue-type plasminogen activator (tPA), but significantly enhanced NF-κB signaling, microglia activation, and the production of pro-inflammatory cytokines in newborn brains. Remarkably, these pathogenic responses were all blocked by intracerebroventricular injection of a stable-mutant form of plasminogen activator protein-1 called CPAI. Similarly, LPS pre-exposure amplified, while CPAI therapy mitigated HI-induced blood-brain-barrier damage and the brain tissue loss with a therapeutic window at 4 h after the LPS/HI insult. The CPAI also blocks microglia activation following a brain injection of LPS, which requires the contribution by tPA, but not the urinary-type plasminogen activator (uPA), as shown by experiments in tPA-null and uPA-null mice. These results implicate the nonproteolytic tPA activity in LPS/HI-induced brain damage and microglia activation. Finally, the CPAI treatment protects near-normal motor and white matter development despite neonatal LPS/HI insult. Together, because CPAI blocks both proteolytic and nonproteolytic tPA neurotoxicity, it is a promising therapeutics of neonatal HI injury either with or without infection.
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