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We recently showed in a rat model of birth asphyxia that seizures are triggered by the post\u2010asphyxia recovery of brain pH. Here our aim was to investigate whether carbonic anhydrase inhibitors (CAIs), which induce systemic acidosis, block the post\u2010asphyxia seizures.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The CAIs acetazolamide (AZA), benzolamide (BZA), and ethoxzolamide (EZA) were administered intraperitoneally or intravenously to 11\u2010day\u2010old rats exposed to intermittent asphyxia (30\u00a0min; three 7+3 min cycles of 9% and 5% O<jats:sub>2<\/jats:sub> at 20% CO<jats:sub>2<\/jats:sub>). Electrode measurements of intracortical pH, <jats:italic>P<\/jats:italic>o<jats:sub>2<\/jats:sub>, and local field potentials (LFPs) were made under urethane anesthesia. Convulsive seizures and blood acid\u2010base parameters were examined in freely behaving animals.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The three CAIs decreased brain pH by 0.14\u20130.17 pH units and suppressed electrographic post\u2010asphyxia seizures. AZA, BZA, and EZA differ greatly in their lipid solubility (EZA &gt; AZA &gt; BZA) and pharmacokinetics. However, there were only minor differences in the delay (range 0.8\u20133.7\u00a0min) from intraperitoneal application to their action on brain pH. The CAIs induced a modest post\u2010asphyxia elevation of brain <jats:italic>P<\/jats:italic>o<jats:sub>2<\/jats:sub> that had no effect on LFP activity. AZA was tested in freely behaving rats, in which it induced a respiratory acidosis and decreased the incidence of convulsive seizures from 9 of 20 to 2 of 17 animals.<\/jats:p><\/jats:sec><jats:sec><jats:title>Significance<\/jats:title><jats:p>AZA, BZA, and EZA effectively block post\u2010asphyxia seizures. Despite the differences in their pharmacokinetics, they had similar effects on brain pH, which indicates that their antiseizure mode of action was based on respiratory (hypercapnic) acidosis resulting from inhibition of blood\u2010borne and extracellular vascular carbonic anhydrases. AZA has been used for several indications in neonates, suggesting that it can be safely repurposed for the treatment of neonatal seizures as an add\u2010on to the current treatment regimen.<\/jats:p><\/jats:sec>","DOI":"10.1111\/epi.16963","type":"journal-article","created":{"date-parts":[[2021,6,28]],"date-time":"2021-06-28T05:41:52Z","timestamp":1624858912000},"page":"1971-1984","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Carbonic anhydrase inhibitors suppress seizures in a rat model of birth asphyxia"],"prefix":"10.1111","volume":"62","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0793-2639","authenticated-orcid":false,"given":"Alexey S.","family":"Pospelov","sequence":"first","affiliation":[{"name":"Faculty of Biological and Environmental Sciences, Molecular and Integrative Biosciences University of Helsinki Helsinki Finland"},{"name":"Neuroscience Center (HiLIFE) University of Helsinki Helsinki 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