{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,23]],"date-time":"2025-11-23T06:16:25Z","timestamp":1763878585042,"version":"3.28.0"},"reference-count":45,"publisher":"Georg Thieme Verlag KG","issue":"11","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Am J Perinatol"],"published-print":{"date-parts":[[2024,8]]},"abstract":"<jats:p>\n            Objective\u2003We aimed to assess the effects of neuroserpin and its combination with hypothermia on hypoxic-ischemic (HI) brain injury in neonatal rats. Neuroserpin is an axon-secreted serine protease inhibitor and is important for brain development, neuronal survival, and synaptic plasticity.<\/jats:p><jats:p>\n            Study Design\u2003Male Wistar\u2013Albino rats on postnatal day 7 (P7) were randomly divided into five groups: sham group (n\u2009=\u200910), (HI; n\u2009=\u200910), hypoxic-ischemic hypothermia (HIH; n\u2009=\u200910), hypoxic-ischemic neuroserpin (HIN; n\u2009=\u200910), and hypoxic-ischemic neuroserpin-hypothermia (HINH; n\u2009=\u200910). The P7 rat brain's maturation is similar to a late preterm human brain at 34 to 36 weeks of gestation. HI was induced in rats on P7 as previously described. A single dose of 0.2 \u00b5M neuroserpin (HINH and HIN) or an equivalent volume of phosphate-buffered saline (sham, HIH, and HI) was administered intraventricularly by a Hamilton syringe immediately after hypoxia. In the follow-up, pups were subjected to systemic hypothermia or normothermia for 2\u2009hours. Euthanasia was performed for histopathological evaluation on P10. Apoptosis was detected by caspase-3 activity and terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) staining and was counted in the hippocampus.<\/jats:p><jats:p>\n            Results\u2003In comparison to the HI group, the TUNEL-positive and caspase-3-positive neurons in the sham, HIN, HIH, and HINH groups were considerably lower (13.4\u2009\u00b1\u20091.0 vs. 1.9\u2009\u00b1\u20090.9, 6.0\u2009\u00b1\u20090.9, 5.3\u2009\u00b1\u20091.6, and 4.0\u2009\u00b1\u20091.1; p\u2009&lt;\u20090.001) and (13.5\u2009\u00b1\u20091.7 vs. 1.2 \u00b1 0.7, 9.1 \u00b1 2.7, 4.8 \u00b1 1.0, and 3.9 \u00b1 1.6; p\u2009&lt;\u20090.001). HIN, HIH, and HINH, compared to the sham group, showed more TUNEL-positive and caspase-3-positive neurons (6.0\u2009\u00b1\u20090.9, 5.3\u2009\u00b1\u20091.6, 4.0\u2009\u00b1\u20091.1 vs. 1.9\u2009\u00b1\u20090.9 and 9.1\u2009\u00b1\u20092.7, 4.8\u2009\u00b1\u20091.0, 3.9\u2009\u00b1\u20091.6 vs. 1.2\u2009\u00b1\u20090.7; p\u2009&lt;\u20090.001). The HINH group (synergistic effect) had significantly fewer TUNEL-positive neurons and caspase-3-positive neurons than the HIN group (4.0\u2009\u00b1\u20091.1 vs. 6.0\u2009\u00b1\u20090.9 and 3.9\u2009\u00b1\u20091.6 vs. 9.1\u2009\u00b1\u20092.7; p\u2009&lt;\u20090.001).<\/jats:p><jats:p>\n            Conclusion\u2003Our study showed that both neuroserpin alone and as an adjuvant treatment for hypothermia may have a neuroprotective effect on brain injury.<\/jats:p><jats:p>\n            Key Points\n          <\/jats:p>","DOI":"10.1055\/a-2159-0488","type":"journal-article","created":{"date-parts":[[2023,8,23]],"date-time":"2023-08-23T23:06:10Z","timestamp":1692831970000},"page":"1538-1543","source":"Crossref","is-referenced-by-count":2,"title":["Neuroserpin As an Adjuvant Therapy for Hypothermia on Brain Injury in Neonatal Hypoxic\u2013Ischemic Rats"],"prefix":"10.1055","volume":"41","author":[{"given":"Hasan","family":"Kilicdag","sequence":"additional","affiliation":[{"name":"Division of Neonatology, Department of Pediatrics, Baskent University Faculty of Medicine, Ankara, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kubra","family":"Akillioglu","sequence":"additional","affiliation":[{"name":"Division of Neurophysiology, Department of Physiology, Medical Faculty, University of Cukurova, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emine","family":"Kilic Bag\u0131r","sequence":"additional","affiliation":[{"name":"Department of Pathology, Cukurova University, Medical Faculty, Adana, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Seda","family":"Kose","sequence":"additional","affiliation":[{"name":"Division of Neurophysiology, Department of Physiology, Medical Faculty, University of Cukurova, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Seyda","family":"Erdogan","sequence":"additional","affiliation":[{"name":"Department of Pathology, Cukurova University, Medical Faculty, Adana, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"194","published-online":{"date-parts":[[2023,9,25]]},"reference":[{"key":"ref1","first-page":"510","volume-title":"Chapter 20\u2014Hypoxic-ischemic injury in the term infant: clinical-neurological features, diagnosis, imaging, prognosis, therapy","author":"T E Inder","year":"2018"},{"issue":"06","key":"ref2","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1016\/j.earlhumdev.2010.05.010","article-title":"Epidemiology of neonatal encephalopathy and hypoxic-ischaemic encephalopathy","volume":"86","author":"J J Kurinczuk","year":"2010","journal-title":"Early Hum Dev"},{"issue":"05","key":"ref3","doi-asserted-by":"crossref","first-page":"410","DOI":"10.1111\/j.1365-3016.2008.00960.x","article-title":"Four million neonatal deaths: counting and attribution of cause of death","volume":"22","author":"J E Lawn","year":"2008","journal-title":"Paediatr Perinat 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