Phenobarbital and midazolam increase neonatal seizure‐associated neuronal injury

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In the neonatal rodent brain, γ‐aminobutyric acidergic (GABAergic) drugs, which are the standard treatment for neonatal seizures, can have excitatory effects, which might aggravate seizures and their long‐term consequences.1 In clinical use and in some experimental models, GABAergic drugs appear to stop behavioral seizures,5 but adverse effects might be hard to detect if they occur in a subpopulation of immature neurons that have little behavioral expression at that age.6 We recently developed a model of status epilepticus (SE) in postnatal day 7 (P7) rat pups that resulted in high survival rates and widespread neuronal injury7 and for the first time offered us the opportunity to test the effect of GABAergic drugs on SE‐associated neuronal injury. We found that both phenobarbital and midazolam treatment of SE increased acute neuronal injury in several brain regions, raising questions about the safety of their clinical use.
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