HIF-1α inhibition ameliorates neonatal brain injury in a rat pup hypoxic–ischemic model
Hypoxia-inducible factor-1alpha (HIF-1α) has been considered as a regulator of both prosurvival and prodeath pathways in the nervous system. The present study was designed to elucidate the role of HIF-1α in neonatal hypoxic–ischemic (HI) brain injury. Rice–Vannucci model of neonatal hypoxic–ischemic...
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| Format: | Article |
| Language: | English |
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Elsevier
2008-09-01
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| Series: | Neurobiology of Disease |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0969996108001241 |
| _version_ | 1818721760796737536 |
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| author | Wanqiu Chen Vikram Jadhav Jiping Tang John H. Zhang |
| author_facet | Wanqiu Chen Vikram Jadhav Jiping Tang John H. Zhang |
| author_sort | Wanqiu Chen |
| collection | DOAJ |
| description | Hypoxia-inducible factor-1alpha (HIF-1α) has been considered as a regulator of both prosurvival and prodeath pathways in the nervous system. The present study was designed to elucidate the role of HIF-1α in neonatal hypoxic–ischemic (HI) brain injury. Rice–Vannucci model of neonatal hypoxic–ischemic brain injury was used in seven-day-old rats, by subjecting unilateral carotid artery ligation followed by 2 h of hypoxia (8% O2 at 37 °C). HIF-1α activity was inhibited by 2-methoxyestradiol (2ME2) and enhanced by dimethyloxalylglycine (DMOG). Results showed that 2ME2 exhibited dose-dependent neuroprotection by decreasing infarct volume and reducing brain edema at 48 h post HI. The neuroprotection was lost when 2ME2 was administered 3 h post HI. HIF-1α upregulation by DMOG increased the permeability of the BBB and brain edema compared with HI group. 2ME2 attenuated the increase in HIF-1α and VEGF 24 h after HI. 2ME2 also had a long-term effect of protecting against the loss of brain tissue. The study showed that the early inhibition of HIF-1α acutely after injury provided neuroprotection after neonatal hypoxia–ischemia which was associated with preservation of BBB integrity, attenuation of brain edema, and neuronal death. |
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| format | Article |
| id | doaj.art-8b95e80a7e4e4849ac1f8aee6bdd75ca |
| institution | Directory Open Access Journal |
| issn | 1095-953X |
| language | English |
| last_indexed | 2024-12-17T20:43:51Z |
| publishDate | 2008-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neurobiology of Disease |
| spelling | doaj.art-8b95e80a7e4e4849ac1f8aee6bdd75ca2022-12-21T21:33:15ZengElsevierNeurobiology of Disease1095-953X2008-09-01313433441HIF-1α inhibition ameliorates neonatal brain injury in a rat pup hypoxic–ischemic modelWanqiu Chen0Vikram Jadhav1Jiping Tang2John H. Zhang3Department of Physiology and Pharmacology, Loma Linda University, School of Medicine, Loma Linda, CA, USADepartment of Physiology and Pharmacology, Loma Linda University, School of Medicine, Loma Linda, CA, USADepartment of Physiology and Pharmacology, Loma Linda University, School of Medicine, Loma Linda, CA, USADepartment of Physiology and Pharmacology, Loma Linda University, School of Medicine, Loma Linda, CA, USA; Department of Neurosurgery, Loma Linda University, School of Medicine, Loma Linda, CA, USA; Corresponding author. Department of Physiology and Pharmacology, Loma Linda University School of Medicine, Risley Hall, Room 214, Loma Linda, California 92350, USA. Fax: +1 909 558 0119.Hypoxia-inducible factor-1alpha (HIF-1α) has been considered as a regulator of both prosurvival and prodeath pathways in the nervous system. The present study was designed to elucidate the role of HIF-1α in neonatal hypoxic–ischemic (HI) brain injury. Rice–Vannucci model of neonatal hypoxic–ischemic brain injury was used in seven-day-old rats, by subjecting unilateral carotid artery ligation followed by 2 h of hypoxia (8% O2 at 37 °C). HIF-1α activity was inhibited by 2-methoxyestradiol (2ME2) and enhanced by dimethyloxalylglycine (DMOG). Results showed that 2ME2 exhibited dose-dependent neuroprotection by decreasing infarct volume and reducing brain edema at 48 h post HI. The neuroprotection was lost when 2ME2 was administered 3 h post HI. HIF-1α upregulation by DMOG increased the permeability of the BBB and brain edema compared with HI group. 2ME2 attenuated the increase in HIF-1α and VEGF 24 h after HI. 2ME2 also had a long-term effect of protecting against the loss of brain tissue. The study showed that the early inhibition of HIF-1α acutely after injury provided neuroprotection after neonatal hypoxia–ischemia which was associated with preservation of BBB integrity, attenuation of brain edema, and neuronal death.http://www.sciencedirect.com/science/article/pii/S0969996108001241Brain edemaHypoxia inducible factorNeonatal hypoxia ischemiaNeuroprotection |
| spellingShingle | Wanqiu Chen Vikram Jadhav Jiping Tang John H. Zhang HIF-1α inhibition ameliorates neonatal brain injury in a rat pup hypoxic–ischemic model Neurobiology of Disease Brain edema Hypoxia inducible factor Neonatal hypoxia ischemia Neuroprotection |
| title | HIF-1α inhibition ameliorates neonatal brain injury in a rat pup hypoxic–ischemic model |
| title_full | HIF-1α inhibition ameliorates neonatal brain injury in a rat pup hypoxic–ischemic model |
| title_fullStr | HIF-1α inhibition ameliorates neonatal brain injury in a rat pup hypoxic–ischemic model |
| title_full_unstemmed | HIF-1α inhibition ameliorates neonatal brain injury in a rat pup hypoxic–ischemic model |
| title_short | HIF-1α inhibition ameliorates neonatal brain injury in a rat pup hypoxic–ischemic model |
| title_sort | hif 1α inhibition ameliorates neonatal brain injury in a rat pup hypoxic ischemic model |
| topic | Brain edema Hypoxia inducible factor Neonatal hypoxia ischemia Neuroprotection |
| url | http://www.sciencedirect.com/science/article/pii/S0969996108001241 |
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