Maternal N-Acetyl-Cysteine Prevents Neonatal Hypoxia-Induced Brain Injury in a Rat Model
Perinatal hypoxia is a major cause of infant brain damage, lifelong neurological disability, and infant mortality. N-Acetyl-Cysteine (NAC) is a powerful antioxidant that acts directly as a scavenger of free radicals. We hypothesized that maternal-antenatal and offspring-postnatal NAC can protect off...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-12-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/24/13629 |
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| author | Ola Gutziet Roee Iluz Hila Ben Asher Linoy Segal Dikla Ben Zvi Yuval Ginsberg Nizar Khatib Osnat Zmora Michael G. Ross Zeev Weiner Ron Beloosesky |
| author_facet | Ola Gutziet Roee Iluz Hila Ben Asher Linoy Segal Dikla Ben Zvi Yuval Ginsberg Nizar Khatib Osnat Zmora Michael G. Ross Zeev Weiner Ron Beloosesky |
| author_sort | Ola Gutziet |
| collection | DOAJ |
| description | Perinatal hypoxia is a major cause of infant brain damage, lifelong neurological disability, and infant mortality. N-Acetyl-Cysteine (NAC) is a powerful antioxidant that acts directly as a scavenger of free radicals. We hypothesized that maternal-antenatal and offspring-postnatal NAC can protect offspring brains from hypoxic brain damage.Sixty six newborn rats were randomized into four study groups. Group 1: Control (CON) received no hypoxic intervention. Group 2: Hypoxia (HYP)-received hypoxia protocol. Group 3: Hypoxia-NAC (HYP-NAC). received hypoxia protocol and treated with NAC following each hypoxia episode. Group 4: NAC Hypoxia (NAC-HYP) treated with NAC during pregnancy, pups subject to hypoxia protocol. Each group was evaluated for: neurological function (Righting reflex), serum proinflammatory IL-6 protein levels (ELISA), brain protein levels: NF-κB p65, neuronal nitric oxide synthase (nNOS), TNF-α, and IL-6 (Western blot) and neuronal apoptosis (histology evaluation with TUNEL stain). Hypoxia significantly increased pups brain protein levels compared to controls. NAC administration to dams or offspring demonstrated lower brain NF-κB p65, nNOS, TNF-α and IL-6 protein levels compared to hypoxia alone. Hypoxia significantly increased brain apoptosis as evidenced by higher grade of brain TUNEL reaction. NAC administration to dams or offspring significantly reduce this effect. Hypoxia induced acute sensorimotor dysfunction. NAC treatment to dams significantly attenuated hypoxia-induced acute sensorimotor dysfunction. Prophylactic NAC treatment of dams during pregnancy confers long-term protection to offspring with hypoxia associated brain injury, measured by several pathways of injury and correlated markers with pathology and behavior. This implies we may consider prophylactic NAC treatment for patients at risk for hypoxia during labor. |
| first_indexed | 2024-03-10T03:54:56Z |
| format | Article |
| id | doaj.art-ba5d0e921476468da2d5b120ac29c630 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T03:54:56Z |
| publishDate | 2021-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-ba5d0e921476468da2d5b120ac29c6302023-11-23T08:49:12ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-12-0122241362910.3390/ijms222413629Maternal N-Acetyl-Cysteine Prevents Neonatal Hypoxia-Induced Brain Injury in a Rat ModelOla Gutziet0Roee Iluz1Hila Ben Asher2Linoy Segal3Dikla Ben Zvi4Yuval Ginsberg5Nizar Khatib6Osnat Zmora7Michael G. Ross8Zeev Weiner9Ron Beloosesky10Department of Obstetrics and Gynecology, Rambam Health Care Campus, Haifa 3525433, IsraelDepartment of Obstetrics and Gynecology, Rambam Health Care Campus, Haifa 3525433, IsraelDepartment of Obstetrics and Gynecology, Rambam Health Care Campus, Haifa 3525433, IsraelDepartment of Obstetrics and Gynecology, Rambam Health Care Campus, Haifa 3525433, IsraelDepartment of Obstetrics and Gynecology, Rambam Health Care Campus, Haifa 3525433, IsraelDepartment of Obstetrics and Gynecology, Rambam Health Care Campus, Haifa 3525433, IsraelDepartment of Obstetrics and Gynecology, Rambam Health Care Campus, Haifa 3525433, IsraelDepartment of Pediatric Surgery, Shamir Medical Center, Tzrifin 7073001, IsraelDepartment of Obstetrics and Gynecology, Harbor-UCLA Medical Center and The Lundquist Institute, Torrance, CA 92270, USADepartment of Obstetrics and Gynecology, Rambam Health Care Campus, Haifa 3525433, IsraelDepartment of Obstetrics and Gynecology, Rambam Health Care Campus, Haifa 3525433, IsraelPerinatal hypoxia is a major cause of infant brain damage, lifelong neurological disability, and infant mortality. N-Acetyl-Cysteine (NAC) is a powerful antioxidant that acts directly as a scavenger of free radicals. We hypothesized that maternal-antenatal and offspring-postnatal NAC can protect offspring brains from hypoxic brain damage.Sixty six newborn rats were randomized into four study groups. Group 1: Control (CON) received no hypoxic intervention. Group 2: Hypoxia (HYP)-received hypoxia protocol. Group 3: Hypoxia-NAC (HYP-NAC). received hypoxia protocol and treated with NAC following each hypoxia episode. Group 4: NAC Hypoxia (NAC-HYP) treated with NAC during pregnancy, pups subject to hypoxia protocol. Each group was evaluated for: neurological function (Righting reflex), serum proinflammatory IL-6 protein levels (ELISA), brain protein levels: NF-κB p65, neuronal nitric oxide synthase (nNOS), TNF-α, and IL-6 (Western blot) and neuronal apoptosis (histology evaluation with TUNEL stain). Hypoxia significantly increased pups brain protein levels compared to controls. NAC administration to dams or offspring demonstrated lower brain NF-κB p65, nNOS, TNF-α and IL-6 protein levels compared to hypoxia alone. Hypoxia significantly increased brain apoptosis as evidenced by higher grade of brain TUNEL reaction. NAC administration to dams or offspring significantly reduce this effect. Hypoxia induced acute sensorimotor dysfunction. NAC treatment to dams significantly attenuated hypoxia-induced acute sensorimotor dysfunction. Prophylactic NAC treatment of dams during pregnancy confers long-term protection to offspring with hypoxia associated brain injury, measured by several pathways of injury and correlated markers with pathology and behavior. This implies we may consider prophylactic NAC treatment for patients at risk for hypoxia during labor.https://www.mdpi.com/1422-0067/22/24/13629hypoxiabrain injuryN-Acetyl Cysteineinflammationoxidative stresssensorimotor dysfunction |
| spellingShingle | Ola Gutziet Roee Iluz Hila Ben Asher Linoy Segal Dikla Ben Zvi Yuval Ginsberg Nizar Khatib Osnat Zmora Michael G. Ross Zeev Weiner Ron Beloosesky Maternal N-Acetyl-Cysteine Prevents Neonatal Hypoxia-Induced Brain Injury in a Rat Model International Journal of Molecular Sciences hypoxia brain injury N-Acetyl Cysteine inflammation oxidative stress sensorimotor dysfunction |
| title | Maternal N-Acetyl-Cysteine Prevents Neonatal Hypoxia-Induced Brain Injury in a Rat Model |
| title_full | Maternal N-Acetyl-Cysteine Prevents Neonatal Hypoxia-Induced Brain Injury in a Rat Model |
| title_fullStr | Maternal N-Acetyl-Cysteine Prevents Neonatal Hypoxia-Induced Brain Injury in a Rat Model |
| title_full_unstemmed | Maternal N-Acetyl-Cysteine Prevents Neonatal Hypoxia-Induced Brain Injury in a Rat Model |
| title_short | Maternal N-Acetyl-Cysteine Prevents Neonatal Hypoxia-Induced Brain Injury in a Rat Model |
| title_sort | maternal n acetyl cysteine prevents neonatal hypoxia induced brain injury in a rat model |
| topic | hypoxia brain injury N-Acetyl Cysteine inflammation oxidative stress sensorimotor dysfunction |
| url | https://www.mdpi.com/1422-0067/22/24/13629 |
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