Mitochondria, Bioenergetics and Excitotoxicity: New Therapeutic Targets in Perinatal Brain Injury
Injury to the fragile immature brain is implicated in the manifestation of long-term neurological disorders, including childhood disability such as cerebral palsy, learning disability and behavioral disorders. Advancements in perinatal practice and improved care mean the majority of infants sufferin...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2017-07-01
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| Series: | Frontiers in Cellular Neuroscience |
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| Online Access: | http://journal.frontiersin.org/article/10.3389/fncel.2017.00199/full |
| _version_ | 1819266152284553216 |
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| author | Bryan Leaw Syam Nair Rebecca Lim Rebecca Lim Claire Thornton Carina Mallard Henrik Hagberg Henrik Hagberg |
| author_facet | Bryan Leaw Syam Nair Rebecca Lim Rebecca Lim Claire Thornton Carina Mallard Henrik Hagberg Henrik Hagberg |
| author_sort | Bryan Leaw |
| collection | DOAJ |
| description | Injury to the fragile immature brain is implicated in the manifestation of long-term neurological disorders, including childhood disability such as cerebral palsy, learning disability and behavioral disorders. Advancements in perinatal practice and improved care mean the majority of infants suffering from perinatal brain injury will survive, with many subtle clinical symptoms going undiagnosed until later in life. Hypoxic-ischemia is the dominant cause of perinatal brain injury, and constitutes a significant socioeconomic burden to both developed and developing countries. Therapeutic hypothermia is the sole validated clinical intervention to perinatal asphyxia; however it is not always neuroprotective and its utility is limited to developed countries. There is an urgent need to better understand the molecular pathways underlying hypoxic-ischemic injury to identify new therapeutic targets in such a small but critical therapeutic window. Mitochondria are highly implicated following ischemic injury due to their roles as the powerhouse and main energy generators of the cell, as well as cell death processes. While the link between impaired mitochondrial bioenergetics and secondary energy failure following loss of high-energy phosphates is well established after hypoxia-ischemia (HI), there is emerging evidence that the roles of mitochondria in disease extend far beyond this. Indeed, mitochondrial turnover, including processes such as mitochondrial biogenesis, fusion, fission and mitophagy, affect recovery of neurons after injury and mitochondria are involved in the regulation of the innate immune response to inflammation. This review article will explore these mitochondrial pathways, and finally will summarize past and current efforts in targeting these pathways after hypoxic-ischemic injury, as a means of identifying new avenues for clinical intervention. |
| first_indexed | 2024-12-23T20:56:44Z |
| format | Article |
| id | doaj.art-3fbeb9c675274d9ea9699c5be4d1cd2c |
| institution | Directory Open Access Journal |
| issn | 1662-5102 |
| language | English |
| last_indexed | 2024-12-23T20:56:44Z |
| publishDate | 2017-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cellular Neuroscience |
| spelling | doaj.art-3fbeb9c675274d9ea9699c5be4d1cd2c2022-12-21T17:31:30ZengFrontiers Media S.A.Frontiers in Cellular Neuroscience1662-51022017-07-011110.3389/fncel.2017.00199277570Mitochondria, Bioenergetics and Excitotoxicity: New Therapeutic Targets in Perinatal Brain InjuryBryan Leaw0Syam Nair1Rebecca Lim2Rebecca Lim3Claire Thornton4Carina Mallard5Henrik Hagberg6Henrik Hagberg7The Ritchie Centre, Hudson Institute of Medical ResearchClayton, VIC, AustraliaPerinatal Center, Institute of Physiology and Neuroscience, Sahlgrenska Academy, University of GothenburgGothenburg, SwedenThe Ritchie Centre, Hudson Institute of Medical ResearchClayton, VIC, AustraliaDepartment of Obstetrics and Gynaecology, Monash University ClaytonClayton, VIC, AustraliaCentre for the Developing Brain, Division of Imaging Sciences and Biomedical Engineering, King’s College London, King’s Health Partners, St. Thomas’ HospitalLondon, United KingdomPerinatal Center, Institute of Physiology and Neuroscience, Sahlgrenska Academy, University of GothenburgGothenburg, SwedenCentre for the Developing Brain, Division of Imaging Sciences and Biomedical Engineering, King’s College London, King’s Health Partners, St. Thomas’ HospitalLondon, United KingdomPerinatal Center, Department of Clinical Sciences, Sahlgrenska Academy, Gothenburg UniversityGothenburg, SwedenInjury to the fragile immature brain is implicated in the manifestation of long-term neurological disorders, including childhood disability such as cerebral palsy, learning disability and behavioral disorders. Advancements in perinatal practice and improved care mean the majority of infants suffering from perinatal brain injury will survive, with many subtle clinical symptoms going undiagnosed until later in life. Hypoxic-ischemia is the dominant cause of perinatal brain injury, and constitutes a significant socioeconomic burden to both developed and developing countries. Therapeutic hypothermia is the sole validated clinical intervention to perinatal asphyxia; however it is not always neuroprotective and its utility is limited to developed countries. There is an urgent need to better understand the molecular pathways underlying hypoxic-ischemic injury to identify new therapeutic targets in such a small but critical therapeutic window. Mitochondria are highly implicated following ischemic injury due to their roles as the powerhouse and main energy generators of the cell, as well as cell death processes. While the link between impaired mitochondrial bioenergetics and secondary energy failure following loss of high-energy phosphates is well established after hypoxia-ischemia (HI), there is emerging evidence that the roles of mitochondria in disease extend far beyond this. Indeed, mitochondrial turnover, including processes such as mitochondrial biogenesis, fusion, fission and mitophagy, affect recovery of neurons after injury and mitochondria are involved in the regulation of the innate immune response to inflammation. This review article will explore these mitochondrial pathways, and finally will summarize past and current efforts in targeting these pathways after hypoxic-ischemic injury, as a means of identifying new avenues for clinical intervention.http://journal.frontiersin.org/article/10.3389/fncel.2017.00199/fullperinatal brain injuryhypoxia-ischemiamitochondrianeuroprotection |
| spellingShingle | Bryan Leaw Syam Nair Rebecca Lim Rebecca Lim Claire Thornton Carina Mallard Henrik Hagberg Henrik Hagberg Mitochondria, Bioenergetics and Excitotoxicity: New Therapeutic Targets in Perinatal Brain Injury Frontiers in Cellular Neuroscience perinatal brain injury hypoxia-ischemia mitochondria neuroprotection |
| title | Mitochondria, Bioenergetics and Excitotoxicity: New Therapeutic Targets in Perinatal Brain Injury |
| title_full | Mitochondria, Bioenergetics and Excitotoxicity: New Therapeutic Targets in Perinatal Brain Injury |
| title_fullStr | Mitochondria, Bioenergetics and Excitotoxicity: New Therapeutic Targets in Perinatal Brain Injury |
| title_full_unstemmed | Mitochondria, Bioenergetics and Excitotoxicity: New Therapeutic Targets in Perinatal Brain Injury |
| title_short | Mitochondria, Bioenergetics and Excitotoxicity: New Therapeutic Targets in Perinatal Brain Injury |
| title_sort | mitochondria bioenergetics and excitotoxicity new therapeutic targets in perinatal brain injury |
| topic | perinatal brain injury hypoxia-ischemia mitochondria neuroprotection |
| url | http://journal.frontiersin.org/article/10.3389/fncel.2017.00199/full |
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