Mitochondria, bioenergetics and excitotoxicity

New therapeutic targets in perinatal brain injury

Bryan Leaw, Syam Nair, Rebecca Lim, Claire Thornton, Carina Mallard, Henrik Hagberg

Research output: Contribution to journalReview ArticleOtherpeer-review

16 Citations (Scopus)

Abstract

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. Hypoxicischemia 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.

Original languageEnglish
Article number199
Number of pages18
JournalFrontiers in Cellular Neuroscience
Volume11
DOIs
Publication statusPublished - 12 Jul 2017

Keywords

  • Hypoxia-ischemia
  • Mitochondria
  • Neuroprotection
  • Perinatal brain injury

Cite this

Leaw, Bryan ; Nair, Syam ; Lim, Rebecca ; Thornton, Claire ; Mallard, Carina ; Hagberg, Henrik. / Mitochondria, bioenergetics and excitotoxicity : New therapeutic targets in perinatal brain injury. In: Frontiers in Cellular Neuroscience. 2017 ; Vol. 11.
@article{c426cec122fe4df59a838ad43560f539,
title = "Mitochondria, bioenergetics and excitotoxicity: New therapeutic targets in perinatal brain injury",
abstract = "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. Hypoxicischemia 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.",
keywords = "Hypoxia-ischemia, Mitochondria, Neuroprotection, Perinatal brain injury",
author = "Bryan Leaw and Syam Nair and Rebecca Lim and Claire Thornton and Carina Mallard and Henrik Hagberg",
year = "2017",
month = "7",
day = "12",
doi = "10.3389/fncel.2017.00199",
language = "English",
volume = "11",
journal = "Frontiers in Cellular Neuroscience",
issn = "1662-5102",
publisher = "Frontiers Media",

}

Mitochondria, bioenergetics and excitotoxicity : New therapeutic targets in perinatal brain injury. / Leaw, Bryan; Nair, Syam; Lim, Rebecca; Thornton, Claire; Mallard, Carina; Hagberg, Henrik.

In: Frontiers in Cellular Neuroscience, Vol. 11, 199, 12.07.2017.

Research output: Contribution to journalReview ArticleOtherpeer-review

TY - JOUR

T1 - Mitochondria, bioenergetics and excitotoxicity

T2 - New therapeutic targets in perinatal brain injury

AU - Leaw, Bryan

AU - Nair, Syam

AU - Lim, Rebecca

AU - Thornton, Claire

AU - Mallard, Carina

AU - Hagberg, Henrik

PY - 2017/7/12

Y1 - 2017/7/12

N2 - 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. Hypoxicischemia 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.

AB - 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. Hypoxicischemia 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.

KW - Hypoxia-ischemia

KW - Mitochondria

KW - Neuroprotection

KW - Perinatal brain injury

UR - http://www.scopus.com/inward/record.url?scp=85026673109&partnerID=8YFLogxK

U2 - 10.3389/fncel.2017.00199

DO - 10.3389/fncel.2017.00199

M3 - Review Article

VL - 11

JO - Frontiers in Cellular Neuroscience

JF - Frontiers in Cellular Neuroscience

SN - 1662-5102

M1 - 199

ER -