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The main points in our response are that (1) our work is on an asphyxia model, not one on \"hypercarbia only\"; (2) clinically relevant parenteral doses of bumetanide applied in vivo lead to concentrations in the brain parenchyma that are at least an order of magnitude lower than what would be sufficient to exert any direct effect\u2014even a transient one\u2014on neuronal functions, including neonatal seizures; and (3) moreover, bumetanide's molecular target in the brain is the Na\u2010K\u20102Cl cotransporter NKCC1, which has vital functions in neurons, astrocytes, and oligodendrocytes as well as microglia. This would make it impossible even for highly brain\u2010permeant NKCC1 blockers to specifically target depolarizing and excitatory actions of \u03b3\u2010aminobutyric acid in principal neurons of the brain, which is postulated as the rationale of clinical trials on neonatal seizures.<\/jats:p>","DOI":"10.1111\/epi.17279","type":"journal-article","created":{"date-parts":[[2022,5,7]],"date-time":"2022-05-07T02:30:31Z","timestamp":1651890631000},"page":"1868-1873","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Bumetanide for neonatal seizures: No light in the pharmacokinetic\/dynamic tunnel"],"prefix":"10.1111","volume":"63","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0668-5955","authenticated-orcid":false,"given":"Kai","family":"Kaila","sequence":"first","affiliation":[{"name":"Molecular and Integrative Biosciences and Neuroscience Center University of Helsinki  Helsinki 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