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Neurosteroid replacement therapy using tiagabine and zuranolone restores cerebellar neurodevelopment and reduces hyperactive behaviour following preterm birth.
J Dev Orig Health Dis
January 2025
School of Biomedical Sciences and Pharmacy, University of Newcastle, Newcastle, Australia.
Preterm birth exposes the neonate to hypoxic-ischaemic and excitotoxic insults that impair neurodevelopment and are magnified by the premature loss of placentally supplied, inhibitory neurosteroids. The cerebellum is a neuronally dense brain region, which undergoes critical periods of development during late gestation, when preterm births frequently occur. We propose that neurosteroid replacement therapy using tiagabine and zuranolone will protect the cerebellum against preterm-associated insults.
View Article and Find Full Text PDFThe Neuroprotective Effects of Caffeine in a Neonatal Hypoxia-Ischemia Model are Regulated through the AMPK/mTOR Pathway.
Int J Biol Sci
January 2025
Department of Neonatology and Pediatric Intensive Care, Children's Hospital University of Bonn, Bonn, Germany.
Article Synopsis
- Neonatal hypoxic-ischemic encephalopathy (HIE) is a leading cause of death and disability in newborns, and caffeine has shown promise in mitigating its effects.
- In a neonatal rat model, caffeine administration post-injury reduced brain damage and inflammation compared to controls, highlighting its potential benefits.
- The study found that caffeine influences the AMPK/mTOR pathway, suggesting that targeting this pathway could enhance neuroprotection and improve outcomes for HIE, especially in regions lacking sufficient resources for treatment.
MRS3997, a dual adenosine A/A receptor agonist, reduces brain ischemic damage and alleviates neuroinflammation in rats.
Neuropharmacology
January 2025
Department of Neuroscience, Psychology, Drug Research and Child Health (NEUROFARBA), Division of Pharmacology and Toxicology, University of Florence, Florence, Italy.
The endogenous neuromodulator adenosine is massively released during hypoxic/ischemic insults and differentially modulates post-ischemic damage depending on the expression and recruitment of its four metabotropic receptor subtypes, namely A, A, A and A receptors (ARs, ARs, ARs and ARs). We previously demonstrated, by using a model of transient middle cerebral artery occlusion (tMCAo) in rats, that selective activation of ARs, as well as ARs, ameliorates post-ischemic brain damage in contrast to neuroinflammation. In the present study, we investigated whether the multitarget nucleoside MRS3997, a full agonist at both ARs and ARs, would afford higher neuroprotection in post-ischemic damage.
View Article and Find Full Text PDFTemporal development of seizure threshold and spontaneous seizures after neonatal asphyxia and the effect of prophylactic treatment with midazolam in rats.
Exp Neurol
January 2025
Department of Pharmacology, Toxicology, and Pharmacy, University of Veterinary Medicine Hannover, Germany; Center for Systems Neuroscience Hannover, Germany; Translational Neuropharmacology Lab, NIFE, Department of Experimental Otology of the ENT Clinics, Hannover Medical School, Hannover, Germany. Electronic address:
Article Synopsis
- Birth asphyxia (BA) can lead to serious complications like hypoxic-ischemic encephalopathy (HIE), resulting in disabilities such as cerebral palsy and epilepsy in infants.
- Researchers used a rat model to investigate the development of epilepsy and the effectiveness of midazolam treatment after BA, finding that seizure occurrence increased significantly over time in untreated rats.
- Midazolam treatment not only reduced spontaneous recurrent seizures in the adult rats but also showed potential protective effects against brain damage and cognitive impairments caused by asphyxia.
Perinatal Caffeine Administration Improves Outcomes in an Ovine Model of Neonatal Hypoxia-Ischemia.
Stroke
November 2024
Department of Pediatrics (J.K.M., Y.W., J.H., A.I., C.H., R.S.H., C.V., H.M., J.L.-B., J.R.F., D.M.F., E.M.), University of California San Francisco.
Article Synopsis
- Neonatal hypoxic-ischemic encephalopathy primarily impacts low- and middle-income countries, with therapeutic hypothermia often proving ineffective, highlighting a need for earlier treatment strategies.
- A study involved administering perinatal caffeine to near-term lambs undergoing severe hypoxia-ischemia, assessing its pharmacokinetics, safety, and efficacy in improving outcomes.
- Caffeine administration enhanced neurodevelopmental results and decreased inflammation and gray matter damage, suggesting it could be a viable treatment for affected neonates compared to previous studies on other medications.
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