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Complex spectrum of phenobarbital effects in a mouse model of neonatal hypoxia-induced seizures. | LitMetric

AI Article Synopsis

  • Seizures in newborns, primarily caused by oxygen deprivation, can damage the brain, and phenobarbital is the main treatment, though its effectiveness and safety are questioned.* -
  • In a mouse study, phenobarbital reduced the frequency of seizures but did not alleviate brain damage or behavioral issues caused by neonatal seizures.* -
  • Interestingly, while phenobarbital didn't correct long-term cognitive deficits, it appeared to lessen brain damage from later seizures triggered by kainic acid.*

Article Abstract

Seizures in neonates, mainly caused by hypoxic-ischemic encephalopathy, are thought to be harmful to the brain. Phenobarbital remains the first line drug therapy for the treatment of suspected neonatal seizures but concerns remain with efficacy and safety. Here we explored the short- and long-term outcomes of phenobarbital treatment in a mouse model of hypoxia-induced neonatal seizures. Seizures were induced in P7 mice by exposure to 5% O for 15 minutes. Immediately after hypoxia, pups received a single dose of phenobarbital (25 mg.kg) or saline. We observed that after administration of phenobarbital seizure burden and number of seizures were reduced compared to the hypoxic period; however, PhB did not suppress acute histopathology. Behavioural analysis of mice at 5 weeks of age previously subjected to hypoxia-seizures revealed an increase in anxiety-like behaviour and impaired memory function compared to control littermates, and these effects were not normalized by phenobarbital. In a seizure susceptibility test, pups previously exposed to hypoxia, with or without phenobarbital, developed longer and more severe seizures in response to kainic acid injection compared to control mice. Unexpectedly, mice treated with phenobarbital developed less hippocampal damage after kainic acid than untreated counterparts. The present study suggests phenobarbital treatment in immature mice does not improve the long lasting functional deficits induces by hypoxia-induced seizures but, unexpectedly, may reduce neuronal death caused by exposure to a second seizure event in later life.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6030182PMC
http://dx.doi.org/10.1038/s41598-018-28044-2DOI Listing

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