ArticleMolecular and cellular neurosciences2014
Erythropoietin attenuates loss of potassium chloride co-transporters following prenatal brain injury.
Article in Molecular and cellular neurosciences, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 57 citations in OpenAlex.
- Preschool Assessment of Preterm Infants Treated With Darbepoetin and Erythropoietin.Pediatrics · 2016Trial
- Elucidating the Pivotal Neuroprotective Mechanisms and Therapeutic Variants of Erythropoietin in Neonatal Brain Injury.Current topics in medicinal chemistry · 2025Review
- CXCR2 immunomodulatory therapy protects against microstructural white matter injury and gait abnormalities but does not mitigate deficits of cognition in a preclinical model of cerebral palsy.Journal of neurochemistry · 2025Article
- Pilot Translational Precision Biobehavioral Assays for Early Detection of Motor Impairments in a Rat Model of Cerebral Palsy.Life (Basel, Switzerland) · 2023Article
- Umbilical cord-derived mesenchymal stromal cell therapy to prevent the development of neurodevelopmental disorders related to low birth weight.Scientific reports · 2023Article
- Traditional and Innovative Anti-seizure Medications Targeting Key Physiopathological Mechanisms: Focus on Neurodevelopment and Neurodegeneration.Current neuropharmacology · 2023Article
- Chorioamnionitis disrupts erythropoietin and melatonin homeostasis through the placental-fetal-brain axis during critical developmental periods.Frontiers in physiology · 2023Article
- Neonatal administration of erythropoietin attenuates cognitive deficits in adult rats following placental insufficiency.Journal of neuroscience research · 2022Article
- Sustained peripheral immune hyper-reactivity (SPIHR): an enduring biomarker of altered inflammatory responses in adult rats after perinatal brain injury.Journal of neuroinflammation · 2021Article
- GABA and glutamate in the preterm neonatal brain: In-vivo measurement by magnetic resonance spectroscopy.NeuroImage · 2021Review
- Preventing Brain Injury in the Preterm Infant-Current Controversies and Potential Therapies.International journal of molecular sciences · 2021Review
- The role of KCC2 in hyperexcitability of the neonatal brain.Neuroscience letters · 2020Article
- Age and Sex Influences Gamma-aminobutyric Acid Concentrations in the Developing Brain of Very Premature Infants.Scientific reports · 2020Article
- Prenatal opioid exposure: The next neonatal neuroinflammatory disease.Brain, behavior, and immunity · 2020Article
- Calpain-2 as a Treatment Target in Prenatal Stress-induced Epileptic Spasms in Infant Rats.Experimental neurobiology · 2019Article
- CXCR2 Blockade Mitigates Neural Cell Injury Following Preclinical Chorioamnionitis.Frontiers in physiology · 2019Article
- Crossing the Chloride Channel: The Current and Potential Therapeutic Value of the Neuronal KBioMed research international · 2019Review
- Dose-dependent reversal of KCC2 hypofunction and phenobarbital-resistant neonatal seizures by ANA12.Scientific reports · 2018Article
- Neonatal erythropoietin mitigates impaired gait, social interaction and diffusion tensor imaging abnormalities in a rat model of prenatal brain injury.Experimental neurology · 2018Article
- The long-term effect of erythropoiesis stimulating agents given to preterm infants: a proton magnetic resonance spectroscopy study on neurometabolites in early childhood.Pediatric radiology · 2018Article
Corrections and comments
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Authors and funding
6 authors at 4 institutions in 1 country.
Funding
Abstract
Therapeutic agents that restore the inhibitory actions of γ-amino butyric acid (GABA) by modulating intracellular chloride concentrations will provide novel avenues to treat stroke, chronic pain, epilepsy, autism, and neurodegenerative and cognitive disorders. During development, upregulation of the potassium-chloride co-transporter KCC2, and the resultant switch from excitatory to inhibitory responses to GABA guide the formation of essential inhibitory circuits. Importantly, maturation of inhibitory mechanisms is also central to the development of excitatory circuits and proper balance between excitatory and inhibitory networks in the developing brain. Loss of KCC2 expression occurs in postmortem samples from human preterm infant brains with white matter lesions. Here we show that late gestation brain injury in a rat model of extreme prematurity impairs the developmental upregulation of potassium chloride co-transporters during a critical postnatal period of circuit maturation in CA3 hippocampus by inducing a sustained loss of oligomeric KCC2 via a calpain-dependent mechanism. Further, administration of erythropoietin (EPO) in a clinically relevant postnatal dosing regimen following the prenatal injury protects the developing brain by reducing calpain activity, restoring oligomeric KCC2 expression and attenuating KCC2 fragmentation, thus providing the first report of a safe therapy to address deficits in KCC2 expression. Together, these data indicate it is possible to reverse abnormalities in KCC2 expression during the postnatal period, and potentially reverse deficits in inhibitory circuit formation central to cognitive impairment and epileptogenesis.
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