{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,23]],"date-time":"2025-10-23T11:04:27Z","timestamp":1761217467642,"version":"3.40.4"},"reference-count":52,"publisher":"S. Karger AG","issue":"3-4","license":[{"start":{"date-parts":[[2011,1,1]],"date-time":"2011-01-01T00:00:00Z","timestamp":1293840000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/karger.com\/pages\/terms-and-conditions"},{"start":{"date-parts":[[2011,1,1]],"date-time":"2011-01-01T00:00:00Z","timestamp":1293840000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/karger.com\/pages\/terms-and-conditions"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Dev Neurosci"],"published-print":{"date-parts":[[2011]]},"abstract":"<jats:p>Striatal neurons are highly vulnerable to hypoxia-ischemia (HI) in term newborns. In a piglet model of HI, striatal neurons develop oxidative stress and organelle disruption by 3\u20136 h of recovery and ischemic cytopathology over 6\u201324 h of recovery. We tested the hypothesis that early treatment with the antioxidants EUK-134 (a manganese-salen derivative that acts as a scavenger of superoxide, hydrogen peroxide, nitric oxide or NO and peroxynitrite) or edaravone (MCI-186, a scavenger of hydroxyl radical and NO) protects striatal neurons from HI. Anesthetized newborn piglets were subjected to 40 min of hypoxia and 7 min of airway occlusion. At 30 min after resuscitation, the piglets received vehicle, EUK-134 or edaravone. Drug treatment did not affect arterial blood pressure, blood gases, blood glucose or rectal temperature. At 4 days of recovery, the density of viable neurons in the putamen of vehicle-treated piglets was 12 \u00b1 6% (\u00b1SD) of sham-operated control density. Treatment with EUK-134 increased viability to 41 \u00b1 17%, and treatment with edaravone increased viability to 39 \u00b1 19%. In the caudate nucleus, neuronal viability was increased from 54 \u00b1 11% in the vehicle group to 78 \u00b1 15% in the EUK-134 group and to 73 \u00b1 13% in the edaravone group. Antioxidant drug treatment accelerated recovery from neurologic deficits and decreased oxidative and nitrative damage to nucleic acids. Treatment with EUK-134 reduced the HI-induced formation of protein carbonyl groups and tyrosine nitration at 3 h of recovery. We conclude that systemic administration of antioxidant agents by 30 min after resuscitation from HI can reduce oxidative stress and salvage neurons in the highly vulnerable striatum in a large-animal model of neonatal HI. Therefore, oxidative stress is an important mechanism for this injury, and antioxidant therapy is a rational, mechanism-based approach to neuroprotection in the newborn brain.<\/jats:p>","DOI":"10.1159\/000327243","type":"journal-article","created":{"date-parts":[[2011,6,24]],"date-time":"2011-06-24T06:16:47Z","timestamp":1308896207000},"page":"299-311","source":"Crossref","is-referenced-by-count":23,"title":["Striatal Neuroprotection from Neonatal Hypoxia-Ischemia in Piglets by Antioxidant Treatment with EUK-134 or Edaravone"],"prefix":"10.1159","volume":"33","author":[{"given":"Xinli","family":"Ni","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zeng-Jin","family":"Yang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Erin L.","family":"Carter","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lee 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