{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,28]],"date-time":"2026-05-28T03:17:04Z","timestamp":1779938224425,"version":"3.53.1"},"reference-count":54,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"5","license":[{"start":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T00:00:00Z","timestamp":1777593600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Stroke"],"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:sec>\n                    <jats:title>BACKGROUND:<\/jats:title>\n                    <jats:p>There is an urgent need for cytoprotective therapies for hypoxic-ischemic encephalopathy in low- and middle-income countries, where therapeutic hypothermia is not beneficial. Infection and inflammation are important risk factors for hypoxic-ischemic encephalopathy in sub-Saharan Africa, and immunomodulatory therapies might improve outcomes. Azithromycin is neuroprotective in rodent hypoxic-ischemic encephalopathy models but validation in large animal models is needed. Our aim was to assess safety and efficacy of intravenous azithromycin after inflammation-amplified hypoxia-ischemia in newborn piglets.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS:<\/jats:title>\n                    <jats:p>\n                      Twenty-five piglets underwent inflammation-amplified hypoxia-ischemia by bilateral carotid artery occlusion and reduction in FiO\n                      <jats:sub>2<\/jats:sub>\n                      to 6% at 4 hours after the start of\n                      <jats:italic toggle=\"yes\">Escherichia coli<\/jats:italic>\n                      liposaccharide infusion (2 mcg\/kg bolus+1 mcg\/kg per hour over 12 hours). At 1 hour after inflammation-amplified hypoxia-ischemia, piglets were randomized to receive vehicle (n=12) or azithromycin 20 mg\/kg over 1 hour (n=13), repeated at 24 and 48 hours. Piglets underwent neurocritical care for 65 hours, including continuous amplitude-integrated encephalography, magnetic resonance imaging\/magnetic resonance spectroscopy at 60 hours, and brain immunohistochemistry. Group differences were evaluated by Bayesian analysis with noninformative priors; the a priori threshold probability of superiority (Pr\n                      <jats:sub>[<\/jats:sub>\n                      <jats:sub>sup]<\/jats:sub>\n                      ) was set at 95%.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS:<\/jats:title>\n                    <jats:p>\n                      Insult severity did not differ between groups. Plasma azithromycin peak concentration (C\n                      <jats:sub>max<\/jats:sub>\n                      ) of \u22482 mg\/mL and brain tissue concentrations of \u22481.5 mg\/kg were achieved. Azithromycin was associated with improved amplitude-integrated encephalography background (Pr\n                      <jats:sub>[<\/jats:sub>\n                      <jats:sub>sup]<\/jats:sub>\n                      =98.6%), an overall increase in neuronal nuclear antigen (NeuN+) cells (Pr\n                      <jats:sub>[<\/jats:sub>\n                      <jats:sub>sup]<\/jats:sub>\n                      =97.8%), increase in Iba1 (ionized calcium-binding adapter molecule 1)+cells (Pr\n                      <jats:sub>[<\/jats:sub>\n                      <jats:sub>sup]<\/jats:sub>\n                      =99.6%) and increase in Iba1 ramification index (resting microglial morphology; Pr\n                      <jats:sub>[<\/jats:sub>\n                      <jats:sub>sup<\/jats:sub>\n                      <jats:sub>]<\/jats:sub>\n                      =99.6%). The treatment benefit on magnetic resonance spectroscopy lactate to N-acetyl aspartate peak area ratio was modest (Pr\n                      <jats:sub>[<\/jats:sub>\n                      <jats:sub>sup]<\/jats:sub>\n                      of 82.7% and 68.5% in the thalamic and white matter voxels, respectively).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSIONS:<\/jats:title>\n                    <jats:p>Azithromycin, administered after inflammation-amplified hypoxia-ischemia was safe and associated with increased neuronal survival, microglial immunomodulation, enhanced amplitude-integrated encephalography recovery, and a modest benefit on lactate to N-acetyl aspartate peak area ratio. These safety and efficacy data of azithromycin as a monotherapy hold promise to improve outcomes for hypoxic-ischemic encephalopathy in low- and middle-income countries.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/strokeaha.125.054318","type":"journal-article","created":{"date-parts":[[2026,2,13]],"date-time":"2026-02-13T10:00:14Z","timestamp":1770976814000},"page":"1362-1375","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":1,"title":["Postnatal Azithromycin Is Neuroprotective and Anti-Inflammatory in a Piglet Model of Hypoxic-Ischemic Encephalopathy"],"prefix":"10.1161","volume":"57","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2004-6650","authenticated-orcid":true,"given":"Raymand","family":"Pang","sequence":"first","affiliation":[{"name":"Department of Neonatology, Institute for Women\u2019s Health, University College London, United Kingdom (R.P., C.M., G.M., Y.K., I.D., A.M., M.H., N.J.R.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher","family":"Meehan","sequence":"additional","affiliation":[{"name":"Department of Neonatology, Institute for Women\u2019s Health, University College London, United Kingdom (R.P., C.M., G.M., Y.K., I.D., A.M., M.H., N.J.R.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-7147-7721","authenticated-orcid":true,"given":"George","family":"Maple","sequence":"additional","affiliation":[{"name":"Department of Neonatology, Institute for Women\u2019s Health, University College London, United Kingdom (R.P., C.M., G.M., Y.K., I.D., A.M., M.H., N.J.R.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-8025-4810","authenticated-orcid":true,"given":"Yujin","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Neonatology, Institute for Women\u2019s Health, University College London, United Kingdom (R.P., C.M., G.M., Y.K., I.D., A.M., M.H., N.J.R.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6815-1428","authenticated-orcid":true,"given":"Ilenia","family":"D\u2019Angelo","sequence":"additional","affiliation":[{"name":"Department of Neonatology, Institute for Women\u2019s Health, University College London, United Kingdom (R.P., C.M., G.M., Y.K., I.D., A.M., M.H., N.J.R.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-9963-0641","authenticated-orcid":true,"given":"Alison","family":"Mintoft","sequence":"additional","affiliation":[{"name":"Department of Neonatology, Institute for Women\u2019s Health, University College London, United Kingdom (R.P., C.M., G.M., Y.K., I.D., A.M., M.H., N.J.R.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-7533-2362","authenticated-orcid":true,"given":"Francisco","family":"Torrealdea","sequence":"additional","affiliation":[{"name":"Medical Physics and Biomedical Engineering, University College London Hospitals, United Kingdom (F.T.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5017-5744","authenticated-orcid":true,"given":"Mariya","family":"Hristova","sequence":"additional","affiliation":[{"name":"Department of Neonatology, Institute for Women\u2019s Health, University College London, United Kingdom (R.P., C.M., G.M., Y.K., I.D., A.M., M.H., N.J.R.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7119-5034","authenticated-orcid":true,"given":"Manjunath P.","family":"Pai","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy, College of Pharmacy (M.P.P.), The 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