Neuroprotective role of nitric oxide inhalation and nitrite in a Neonatal Rat Model of Hypoxic-Ischemic Injury.
<h4>Background</h4>There is evidence from various models of hypoxic-ischemic injury (HII) that nitric oxide (NO) is protective. We hypothesized that either inhaled NO (iNO) or nitrite would alleviate brain injury in neonatal HII via modulation of mitochondrial function.<h4>Methods&...
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Public Library of Science (PLoS)
2022-01-01
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| Online Access: | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0268282&type=printable |
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| author | Peter Jung Euntaik Ha Meijuan Zhang Carolyn Fall Mindy Hwang Emily Taylor Samuel Stetkevich Aditi Bhanot Christopher G Wilson Johnny D Figueroa Andre Obenaus Shannon Bragg Beatriz Tone Saburi Eliamani Barbara Holshouser Arlin B Blood Taiming Liu |
| author_facet | Peter Jung Euntaik Ha Meijuan Zhang Carolyn Fall Mindy Hwang Emily Taylor Samuel Stetkevich Aditi Bhanot Christopher G Wilson Johnny D Figueroa Andre Obenaus Shannon Bragg Beatriz Tone Saburi Eliamani Barbara Holshouser Arlin B Blood Taiming Liu |
| author_sort | Peter Jung |
| collection | DOAJ |
| description | <h4>Background</h4>There is evidence from various models of hypoxic-ischemic injury (HII) that nitric oxide (NO) is protective. We hypothesized that either inhaled NO (iNO) or nitrite would alleviate brain injury in neonatal HII via modulation of mitochondrial function.<h4>Methods</h4>We tested the effects of iNO and nitrite on the Rice-Vannucci model of HII in 7-day-old rats. Brain mitochondria were isolated for flow cytometry, aconitase activity, electron paramagnetic resonance, and Seahorse assays.<h4>Results</h4>Pretreatment of pups with iNO decreased survival in the Rice-Vannucci model of HII, while iNO administered post-insult did not. MRI analysis demonstrated that pre-HII iNO at 40 ppm and post-HII iNO at 20 ppm decreased the brain lesion sizes from 6.3±1.3% to 1.0±0.4% and 1.8±0.8%, respectively. Intraperitoneal nitrite at 0.165 μg/g improved neurobehavioral performance but was harmful at higher doses and had no effect on brain infarct size. NO reacted with complex IV at the heme a3 site, decreased the oxidative stress of mitochondria challenged with anoxia and reoxygenation, and suppressed mitochondrial oxygen respiration.<h4>Conclusions</h4>This study suggests that iNO administered following neonatal HII may be neuroprotective, possibly via its modulation of mitochondrial function. |
| format | Article |
| id | doaj-art-15e8e2de73e6447fa8159ade077c977b |
| institution | Kabale University |
| issn | 1932-6203 |
| language | English |
| publishDate | 2022-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj-art-15e8e2de73e6447fa8159ade077c977b2025-01-21T05:31:28ZengPublic Library of Science (PLoS)PLoS ONE1932-62032022-01-01175e026828210.1371/journal.pone.0268282Neuroprotective role of nitric oxide inhalation and nitrite in a Neonatal Rat Model of Hypoxic-Ischemic Injury.Peter JungEuntaik HaMeijuan ZhangCarolyn FallMindy HwangEmily TaylorSamuel StetkevichAditi BhanotChristopher G WilsonJohnny D FigueroaAndre ObenausShannon BraggBeatriz ToneSaburi EliamaniBarbara HolshouserArlin B BloodTaiming Liu<h4>Background</h4>There is evidence from various models of hypoxic-ischemic injury (HII) that nitric oxide (NO) is protective. We hypothesized that either inhaled NO (iNO) or nitrite would alleviate brain injury in neonatal HII via modulation of mitochondrial function.<h4>Methods</h4>We tested the effects of iNO and nitrite on the Rice-Vannucci model of HII in 7-day-old rats. Brain mitochondria were isolated for flow cytometry, aconitase activity, electron paramagnetic resonance, and Seahorse assays.<h4>Results</h4>Pretreatment of pups with iNO decreased survival in the Rice-Vannucci model of HII, while iNO administered post-insult did not. MRI analysis demonstrated that pre-HII iNO at 40 ppm and post-HII iNO at 20 ppm decreased the brain lesion sizes from 6.3±1.3% to 1.0±0.4% and 1.8±0.8%, respectively. Intraperitoneal nitrite at 0.165 μg/g improved neurobehavioral performance but was harmful at higher doses and had no effect on brain infarct size. NO reacted with complex IV at the heme a3 site, decreased the oxidative stress of mitochondria challenged with anoxia and reoxygenation, and suppressed mitochondrial oxygen respiration.<h4>Conclusions</h4>This study suggests that iNO administered following neonatal HII may be neuroprotective, possibly via its modulation of mitochondrial function.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0268282&type=printable |
| spellingShingle | Peter Jung Euntaik Ha Meijuan Zhang Carolyn Fall Mindy Hwang Emily Taylor Samuel Stetkevich Aditi Bhanot Christopher G Wilson Johnny D Figueroa Andre Obenaus Shannon Bragg Beatriz Tone Saburi Eliamani Barbara Holshouser Arlin B Blood Taiming Liu Neuroprotective role of nitric oxide inhalation and nitrite in a Neonatal Rat Model of Hypoxic-Ischemic Injury. PLoS ONE |
| title | Neuroprotective role of nitric oxide inhalation and nitrite in a Neonatal Rat Model of Hypoxic-Ischemic Injury. |
| title_full | Neuroprotective role of nitric oxide inhalation and nitrite in a Neonatal Rat Model of Hypoxic-Ischemic Injury. |
| title_fullStr | Neuroprotective role of nitric oxide inhalation and nitrite in a Neonatal Rat Model of Hypoxic-Ischemic Injury. |
| title_full_unstemmed | Neuroprotective role of nitric oxide inhalation and nitrite in a Neonatal Rat Model of Hypoxic-Ischemic Injury. |
| title_short | Neuroprotective role of nitric oxide inhalation and nitrite in a Neonatal Rat Model of Hypoxic-Ischemic Injury. |
| title_sort | neuroprotective role of nitric oxide inhalation and nitrite in a neonatal rat model of hypoxic ischemic injury |
| url | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0268282&type=printable |
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