ArticleDevelopmental neuroscience2011
Inhibition of X-linked inhibitor of apoptosis with embelin differentially affects male versus female behavioral outcome following neonatal hypoxia-ischemia in rats.
Article in Developmental neuroscience, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 45 citations in OpenAlex.
- A Novel Approach of Development of Robust Animal Model for Autism Spectrum Disorder.Annals of neurosciences · 2026Article
- Sex dimorphism in brain cell death after hypoxia-ischemia in newborn piglets.Pediatric research · 2025Article
- Hypoxia-ischemia and sexual dimorphism: modeling mitochondrial dysfunction using brain organoids.Cell & bioscience · 2025Review
- Structural and Functional Effects of C5aR1 Antagonism in a Rat Model of Neonatal Hypoxic-Ischemic Encephalopathy.Developmental neuroscience · 2025Article
- Advanced age and female sex protect cerebral arteries from mitochondrial depolarization and apoptosis during acute oxidative stress.Aging cell · 2024Article
- URB447 Is Neuroprotective in Both Male and Female Rats after Neonatal Hypoxia-Ischemia and Enhances Neurogenesis in Females.International journal of molecular sciences · 2024Article
- Therapeutic Interventions in Rat Models of Preterm Hypoxic Ischemic Injury: Effects of Hypothermia, Caffeine, and the Influence of Sex.Life (Basel, Switzerland) · 2022Review
- Reviewing the Traditional/Modern Uses, Phytochemistry, Essential Oils/Extracts and Pharmacology ofAntioxidants (Basel, Switzerland) · 2022Review
- Novel Injury Scoring Tool for Assessing Brain Injury following Neonatal Hypoxia-Ischemia in Mice.Developmental neuroscience · 2022Article
- Umbilical cord blood therapy modulates neonatal hypoxic ischemic brain injury in both females and males.Scientific reports · 2021Article
- Sex-related differences in arterial spin-labelled perfusion of metabolically active brain structures in neonatal hypoxic-ischaemic encephalopathy.Clinical radiology · 2021Article
- Androgens and the developing hippocampus.Biology of sex differences · 2020Review
- Early postnatal hypoxia induces behavioral deficits but not morphological damage in the hippocampus in adolescent rats.Physiological research · 2020Article
- Hypoxia-Ischemia and Hypothermia Independently and Interactively Affect Neuronal Pathology in Neonatal Piglets with Short-Term Recovery.Developmental neuroscience · 2019Article
- X-linked inhibitor of apoptosis inhibits apoptosis and preserves the blood-brain barrier after experimental subarachnoid hemorrhage.Scientific reports · 2017Article
- Plant Derived Phytocompound, Embelin in CNS Disorders: A Systematic Review.Frontiers in pharmacology · 2017Review
- Neonatal Hypoxia Ischaemia: Mechanisms, Models, and Therapeutic Challenges.Frontiers in cellular neuroscience · 2017Review
- Sex-dependent mitophagy and neuronal death following rat neonatal hypoxia-ischemia.Neuroscience · 2016Article
- Sex differences in cell genesis, hippocampal volume and behavioral outcomes in a rat model of neonatal HI.Experimental neurology · 2016Article
- Sex differences in behavioral outcomes following temperature modulation during induced neonatal hypoxic ischemic injury in rats.Brain sciences · 2015Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Hypoxia-ischemia (HI; concurrent oxygen/blood deficiency) and associated encephalopathy represent a common cause of neurological injury in premature/low-birth-weight infants and term infants with birth complications. Resulting behavioral impairments include cognitive and/or sensory processing deficits, as well as language disabilities, and clinical evidence shows that male infants with HI exhibit more severe cognitive deficits compared to females with equivalent injury. Evidence also demonstrates activation of sex-dependent apoptotic pathways following HI events, with males preferentially activating a caspase-independent cascade of cell death and females preferentially activating a caspase-dependent cascade following neonatal hypoxic and/or ischemic insults. Based on these combined data, the 'female protection' following HI injury may reflect the endogenous X-linked inhibitor of apoptosis (XIAP), which effectively binds effector caspases and halts downstream cleavage of effector caspases (thus reducing cell death). To test this theory, the current study utilized neonatal injections of vehicle or embelin (a small molecule inhibitor of XIAP) in male and female rats with or without induced HI injury on postnatal day 7 (P7). Subsequent behavioral testing using a clinically relevant task revealed that the inhibition of XIAP exacerbated HI-induced persistent behavioral deficits in females, with no effect on HI males. These results support sex differences in mechanisms of cell death following early HI injuries, and suggest a potential clinical benefit from the development of sex-specific neuroprotectants for the treatment of HI.
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