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Death of hippocampal pyramidal cells occurs acutely after HI, but characterization of delayed cell death and injury of interneurons (INs) is unknown. We hypothesize that injury of INs after HI is: (i) asynchronous to that of pyramidal cells, (ii) independent of injury severity, and (iii) unresponsive to TH. HI was induced in C57BL6 mice at p10 with unilateral right carotid ligation and 45\u2009min of hypoxia (FiO<jats:sub>2<\/jats:sub>\u2009=\u20090.08). Mice were randomized to normothermia (36\u2009\u00b0C, NT) or TH (31\u2009\u00b0C) for 4\u2009hr after HI and anesthesia\u2010exposed shams were use as controls. Brains were studied at 24\u2009hr (p11) or 8 days (p18) after HI. Vglut1, GAD65\/67, PSD95, parvalbumin (PV) and calbindin\u20101 (Calb1) were measured. Cell death was assessed using cresyl violet staining and TUNEL assay. Hippocampal atrophy and astroglyosis at p18 were used to assess injury severity and to correlate with number of PV\u2009+\u2009INs. VGlut1 level decreased by 30% at 24\u2009hr after HI, while GAD65\/67 level decreased by \u223c50% in forebrain 8 days after HI, a decrease localized in CA1 and CA3. PSD95 levels decreased in forebrain by 65% at 24\u2009hr after HI and remained low 8 days after HI. PV\u2009+\u2009INs increased in numbers (per mm<jats:sup>2<\/jats:sup>) and branching between p11 and p18 in sham mice but not in NT and TH mice, resulting in 21\u201352% fewer PV\u2009+\u2009INs in injured mice at p18. Calb1 protein and mRNA were also reduced in HI injured mice at p18. At p18, somatodendritic attrition of INs was evident in all injured mice without evidence of cell death. Neither hippocampal atrophy nor astroglyosis correlated with the number of PV\u2009+\u2009INs at p18. Thus, HI exposure has long lasting effects in the hippocampus impairing the development of the GABAergic system with only partial protection by TH independent of the degree of hippocampal injury. \u00a9 2018 Wiley Periodicals, Inc.<\/jats:p>","DOI":"10.1002\/hipo.22965","type":"journal-article","created":{"date-parts":[[2018,5,21]],"date-time":"2018-05-21T08:50:42Z","timestamp":1526892642000},"page":"617-630","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":51,"title":["Delayed injury of hippocampal interneurons after neonatal hypoxia\u2010ischemia and therapeutic hypothermia in a murine model"],"prefix":"10.1002","volume":"28","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0788-8028","authenticated-orcid":false,"given":"Raul","family":"Chavez\u2010Valdez","sequence":"first","affiliation":[{"name":"Division of Neonatal\u2010Perinatal Medicine, Department of Pediatrics, Johns Hopkins School of Medicine  Baltimore Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Emerson","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, The Zanvyl Krieger Mind\/Brain Institute Johns Hopkins University  Baltimore Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janasha","family":"Goffigan\u2010Holmes","sequence":"additional","affiliation":[{"name":"Division of Neonatal\u2010Perinatal Medicine, Department of Pediatrics, Johns Hopkins School of Medicine  Baltimore Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alfredo","family":"Kirkwood","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, The Zanvyl Krieger Mind\/Brain Institute Johns Hopkins University  Baltimore Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lee J.","family":"Martin","sequence":"additional","affiliation":[{"name":"Department of Neuroscience Johns Hopkins School of Medicine  Baltimore Maryland"},{"name":"Department of Pathology Johns Hopkins School of Medicine  Baltimore Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frances J.","family":"Northington","sequence":"additional","affiliation":[{"name":"Division of Neonatal\u2010Perinatal Medicine, Department of Pediatrics, Johns Hopkins School of Medicine  Baltimore Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,9,11]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/mrm.24956"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1315788"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1080\/09297049.2011.613815"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0893-133X(01)00225-1"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1152\/jn.00084.2005"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/0003-2697(76)90527-3"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2012.00065"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0118889"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpeds.2013.10.067"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2012.05.002"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2013.12.023"},{"issue":"24","key":"e_1_2_9_13_1","first-page":"3391","article-title":"Investigation of the course of GFAP in blood in the initial 24 hours in rats subjected to minor head trauma","volume":"17","author":"Cikriklar H. 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