Early Detection of Hypothermic Neuroprotection Using T2-Weighted Magnetic Resonance Imaging in a Mouse Model of Hypoxic Ischemic Encephalopathy
Perinatal hypoxic-ischemic encephalopathy (HIE) can lead to neurodevelopmental disorders, including cerebral palsy. Standard care for neonatal HIE includes therapeutic hypothermia, which provides partial neuroprotection; magnetic resonance imaging (MRI) is often used to assess injury and predict out...
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2018-05-01
|
| Series: | Frontiers in Neurology |
| Subjects: | |
| Online Access: | http://journal.frontiersin.org/article/10.3389/fneur.2018.00304/full |
| _version_ | 1818590271536889856 |
|---|---|
| author | Sydney E. Doman Akanksha Girish Christina L. Nemeth Gabrielle T. Drummond Patrice Carr Maxine S. Garcia Michael V. Johnston Michael V. Johnston Sujatha Kannan Sujatha Kannan Ali Fatemi Ali Fatemi Jiangyang Zhang Mary Ann Wilson Mary Ann Wilson Mary Ann Wilson |
| author_facet | Sydney E. Doman Akanksha Girish Christina L. Nemeth Gabrielle T. Drummond Patrice Carr Maxine S. Garcia Michael V. Johnston Michael V. Johnston Sujatha Kannan Sujatha Kannan Ali Fatemi Ali Fatemi Jiangyang Zhang Mary Ann Wilson Mary Ann Wilson Mary Ann Wilson |
| author_sort | Sydney E. Doman |
| collection | DOAJ |
| description | Perinatal hypoxic-ischemic encephalopathy (HIE) can lead to neurodevelopmental disorders, including cerebral palsy. Standard care for neonatal HIE includes therapeutic hypothermia, which provides partial neuroprotection; magnetic resonance imaging (MRI) is often used to assess injury and predict outcome after HIE. Immature rodent models of HIE are used to evaluate mechanisms of injury and to examine the efficacy and mechanisms of neuroprotective interventions such as hypothermia. In this study, we first confirmed that, in the CD1 mouse model of perinatal HIE used for our research, MRI obtained 3 h after hypoxic ischemia (HI) could reliably assess initial brain injury and predict histopathological outcome. Mice were subjected to HI (unilateral carotid ligation followed by exposure to hypoxia) on postnatal day 7 and were imaged with T2-weighted MRI and diffusion-weighted MRI (DWI), 3 h after HI. Clearly defined regions of increased signal were comparable in T2 MRI and DWI, and we found a strong correlation between T2 MRI injury scores 3 h after HI and histopathological brain injury 7 days after HI, validating this method for evaluating initial injury in this model of HIE. The more efficient, higher resolution T2 MRI was used to score initial brain injury in subsequent studies. In mice treated with hypothermia, we found a significant reduction in T2 MRI injury scores 3 h after HI, compared to normothermic littermates. Early hypothermic neuroprotection was maintained 7 days after HI, in both T2 MRI injury scores and histopathology. In the normothermic group, T2 MRI injury scores 3 h after HI were comparable to those obtained 7 days after HI. However, in the hypothermic group, brain injury was significantly less 7 days after HI than at 3 h. Thus, early neuroprotective effects of hypothermia were enhanced by 7 days, which may reflect the additional 3 h of hypothermia after imaging or effects on later mechanisms of injury, such as delayed cell death and inflammation. Our results demonstrate that hypothermia has early neuroprotective effects in this model. These findings suggest that hypothermia has an impact on early mechanisms of excitotoxic injury and support initiation of hypothermic intervention as soon as possible after diagnosis of HIE. |
| first_indexed | 2024-12-16T09:53:54Z |
| format | Article |
| id | doaj.art-4e25e385b29c40539560e05fe0b84a12 |
| institution | Directory Open Access Journal |
| issn | 1664-2295 |
| language | English |
| last_indexed | 2024-12-16T09:53:54Z |
| publishDate | 2018-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Neurology |
| spelling | doaj.art-4e25e385b29c40539560e05fe0b84a122022-12-21T22:35:58ZengFrontiers Media S.A.Frontiers in Neurology1664-22952018-05-01910.3389/fneur.2018.00304349370Early Detection of Hypothermic Neuroprotection Using T2-Weighted Magnetic Resonance Imaging in a Mouse Model of Hypoxic Ischemic EncephalopathySydney E. Doman0Akanksha Girish1Christina L. Nemeth2Gabrielle T. Drummond3Patrice Carr4Maxine S. Garcia5Michael V. Johnston6Michael V. Johnston7Sujatha Kannan8Sujatha Kannan9Ali Fatemi10Ali Fatemi11Jiangyang Zhang12Mary Ann Wilson13Mary Ann Wilson14Mary Ann Wilson15Hugo W. Moser Research Institute at Kennedy Krieger, Baltimore, MD, United StatesHugo W. Moser Research Institute at Kennedy Krieger, Baltimore, MD, United StatesHugo W. Moser Research Institute at Kennedy Krieger, Baltimore, MD, United StatesHugo W. Moser Research Institute at Kennedy Krieger, Baltimore, MD, United StatesHugo W. Moser Research Institute at Kennedy Krieger, Baltimore, MD, United StatesHugo W. Moser Research Institute at Kennedy Krieger, Baltimore, MD, United StatesHugo W. Moser Research Institute at Kennedy Krieger, Baltimore, MD, United StatesDepartment of Neurology, The Johns Hopkins University School of Medicine, Baltimore, MD, United StatesHugo W. Moser Research Institute at Kennedy Krieger, Baltimore, MD, United StatesAnesthesiology and Critical Care Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD, United StatesHugo W. Moser Research Institute at Kennedy Krieger, Baltimore, MD, United StatesDepartment of Neurology, The Johns Hopkins University School of Medicine, Baltimore, MD, United StatesDepartment of Radiology, New York University School of Medicine, New York, NY, United StatesHugo W. Moser Research Institute at Kennedy Krieger, Baltimore, MD, United StatesDepartment of Neurology, The Johns Hopkins University School of Medicine, Baltimore, MD, United StatesDepartment of Neuroscience, The Johns Hopkins University School of Medicine, Baltimore, MD, United StatesPerinatal hypoxic-ischemic encephalopathy (HIE) can lead to neurodevelopmental disorders, including cerebral palsy. Standard care for neonatal HIE includes therapeutic hypothermia, which provides partial neuroprotection; magnetic resonance imaging (MRI) is often used to assess injury and predict outcome after HIE. Immature rodent models of HIE are used to evaluate mechanisms of injury and to examine the efficacy and mechanisms of neuroprotective interventions such as hypothermia. In this study, we first confirmed that, in the CD1 mouse model of perinatal HIE used for our research, MRI obtained 3 h after hypoxic ischemia (HI) could reliably assess initial brain injury and predict histopathological outcome. Mice were subjected to HI (unilateral carotid ligation followed by exposure to hypoxia) on postnatal day 7 and were imaged with T2-weighted MRI and diffusion-weighted MRI (DWI), 3 h after HI. Clearly defined regions of increased signal were comparable in T2 MRI and DWI, and we found a strong correlation between T2 MRI injury scores 3 h after HI and histopathological brain injury 7 days after HI, validating this method for evaluating initial injury in this model of HIE. The more efficient, higher resolution T2 MRI was used to score initial brain injury in subsequent studies. In mice treated with hypothermia, we found a significant reduction in T2 MRI injury scores 3 h after HI, compared to normothermic littermates. Early hypothermic neuroprotection was maintained 7 days after HI, in both T2 MRI injury scores and histopathology. In the normothermic group, T2 MRI injury scores 3 h after HI were comparable to those obtained 7 days after HI. However, in the hypothermic group, brain injury was significantly less 7 days after HI than at 3 h. Thus, early neuroprotective effects of hypothermia were enhanced by 7 days, which may reflect the additional 3 h of hypothermia after imaging or effects on later mechanisms of injury, such as delayed cell death and inflammation. Our results demonstrate that hypothermia has early neuroprotective effects in this model. These findings suggest that hypothermia has an impact on early mechanisms of excitotoxic injury and support initiation of hypothermic intervention as soon as possible after diagnosis of HIE.http://journal.frontiersin.org/article/10.3389/fneur.2018.00304/fullhypothermianeuroprotectionhypoxic-ischemicneonatal encephalopathymagnetic resonance imaging |
| spellingShingle | Sydney E. Doman Akanksha Girish Christina L. Nemeth Gabrielle T. Drummond Patrice Carr Maxine S. Garcia Michael V. Johnston Michael V. Johnston Sujatha Kannan Sujatha Kannan Ali Fatemi Ali Fatemi Jiangyang Zhang Mary Ann Wilson Mary Ann Wilson Mary Ann Wilson Early Detection of Hypothermic Neuroprotection Using T2-Weighted Magnetic Resonance Imaging in a Mouse Model of Hypoxic Ischemic Encephalopathy Frontiers in Neurology hypothermia neuroprotection hypoxic-ischemic neonatal encephalopathy magnetic resonance imaging |
| title | Early Detection of Hypothermic Neuroprotection Using T2-Weighted Magnetic Resonance Imaging in a Mouse Model of Hypoxic Ischemic Encephalopathy |
| title_full | Early Detection of Hypothermic Neuroprotection Using T2-Weighted Magnetic Resonance Imaging in a Mouse Model of Hypoxic Ischemic Encephalopathy |
| title_fullStr | Early Detection of Hypothermic Neuroprotection Using T2-Weighted Magnetic Resonance Imaging in a Mouse Model of Hypoxic Ischemic Encephalopathy |
| title_full_unstemmed | Early Detection of Hypothermic Neuroprotection Using T2-Weighted Magnetic Resonance Imaging in a Mouse Model of Hypoxic Ischemic Encephalopathy |
| title_short | Early Detection of Hypothermic Neuroprotection Using T2-Weighted Magnetic Resonance Imaging in a Mouse Model of Hypoxic Ischemic Encephalopathy |
| title_sort | early detection of hypothermic neuroprotection using t2 weighted magnetic resonance imaging in a mouse model of hypoxic ischemic encephalopathy |
| topic | hypothermia neuroprotection hypoxic-ischemic neonatal encephalopathy magnetic resonance imaging |
| url | http://journal.frontiersin.org/article/10.3389/fneur.2018.00304/full |
| work_keys_str_mv | AT sydneyedoman earlydetectionofhypothermicneuroprotectionusingt2weightedmagneticresonanceimaginginamousemodelofhypoxicischemicencephalopathy AT akankshagirish earlydetectionofhypothermicneuroprotectionusingt2weightedmagneticresonanceimaginginamousemodelofhypoxicischemicencephalopathy AT christinalnemeth earlydetectionofhypothermicneuroprotectionusingt2weightedmagneticresonanceimaginginamousemodelofhypoxicischemicencephalopathy AT gabrielletdrummond earlydetectionofhypothermicneuroprotectionusingt2weightedmagneticresonanceimaginginamousemodelofhypoxicischemicencephalopathy AT patricecarr earlydetectionofhypothermicneuroprotectionusingt2weightedmagneticresonanceimaginginamousemodelofhypoxicischemicencephalopathy AT maxinesgarcia earlydetectionofhypothermicneuroprotectionusingt2weightedmagneticresonanceimaginginamousemodelofhypoxicischemicencephalopathy AT michaelvjohnston earlydetectionofhypothermicneuroprotectionusingt2weightedmagneticresonanceimaginginamousemodelofhypoxicischemicencephalopathy AT michaelvjohnston earlydetectionofhypothermicneuroprotectionusingt2weightedmagneticresonanceimaginginamousemodelofhypoxicischemicencephalopathy AT sujathakannan earlydetectionofhypothermicneuroprotectionusingt2weightedmagneticresonanceimaginginamousemodelofhypoxicischemicencephalopathy AT sujathakannan earlydetectionofhypothermicneuroprotectionusingt2weightedmagneticresonanceimaginginamousemodelofhypoxicischemicencephalopathy AT alifatemi earlydetectionofhypothermicneuroprotectionusingt2weightedmagneticresonanceimaginginamousemodelofhypoxicischemicencephalopathy AT alifatemi earlydetectionofhypothermicneuroprotectionusingt2weightedmagneticresonanceimaginginamousemodelofhypoxicischemicencephalopathy AT jiangyangzhang earlydetectionofhypothermicneuroprotectionusingt2weightedmagneticresonanceimaginginamousemodelofhypoxicischemicencephalopathy AT maryannwilson earlydetectionofhypothermicneuroprotectionusingt2weightedmagneticresonanceimaginginamousemodelofhypoxicischemicencephalopathy AT maryannwilson earlydetectionofhypothermicneuroprotectionusingt2weightedmagneticresonanceimaginginamousemodelofhypoxicischemicencephalopathy AT maryannwilson earlydetectionofhypothermicneuroprotectionusingt2weightedmagneticresonanceimaginginamousemodelofhypoxicischemicencephalopathy |