Reply to the commentary by Ben-Ari and Delpire: Bumetanide and neonatal seizures: Fiction versus reality.

In this response to a commentary by Ben-Ari and Delpire on our recent study on the pharmacology of neonatal seizures in a novel, physiologically validated rat model of birth asphyxia, we wish to rectify their inaccurate descriptions of our model and data. Furthermore, because Ben-Ari and Delpire suggest that negative data on bumetanide from preclinical and clinical trials of neonatal seizures have few implications for (alleged) bumetanide actions on neurons in other brain disorders, we will discuss this topic as well. Based on the poor brain penetration of bumetanide, combined with the extremely wide cellular expression patterns of the target protein NKCC1, it is obvious that the numerous actions of systemically applied bumetanide described in the literature are not mediated by the drug's effects on central neurons.