Neuronal cell death in neonatal hypoxia-ischemia
Reads0
Chats0
TLDR
It is conceptualized based on morphological and biochemical data that this degeneration is better classified according to an apoptosis‐necrosis cell death continuum and that programmed cell necrosis has prominent contribution in the neurodegeneration of HIE in animal models.Abstract:
Perinatal hypoxic-ischemic encephalopathy (HIE) is a significant cause of mortality and morbidity in infants and young children. Therapeutic opportunities are very limited for neonatal and pediatric HIE. Specific neural systems and populations of cells are selectively vulnerable in HIE; however, the mechanisms of degeneration are unresolved. These mechanisms involve oxidative stress, excitotoxicity, inflammation, and the activation of several different cell death pathways. Decades ago the structural and mechanistic basis of the cellular degeneration in HIE was thought to be necrosis. Subsequently, largely due to advances in cell biology and to experimental animal studies, emphasis has been switched to apoptosis or autophagy mediated by programmed cell death (PCD) mechanisms as important forms of degeneration in HIE. We have conceptualized based on morphological and biochemical data that this degeneration is better classified according to an apoptosis-necrosis cell death continuum and that programmed cell necrosis has prominent contribution in the neurodegeneration of HIE in animal models. It is likely that neonatal HIE evolves through many cell death chreodes influenced by the dynamic injury landscape. The relevant injury mechanisms remain to be determined in human neonatal HIE, though preliminary work suggests a complexity in the cell death mechanisms greater than that anticipated from experimental animal models. The accurate identification of the various cell death chreodes and their mechanisms unfolding within the immature brain matrix could provide fresh insight for developing meaningful therapies for neonatal and pediatric HIE.read more
Citations
More filters
Journal ArticleDOI
Epigenetic Regulation of Motor Neuron Cell Death Through DNA Methylation
TL;DR: Motor neurons can engage epigenetic mechanisms to drive apoptosis, involving Dnmt upregulation and increased DNA methylation, and these cellular mechanisms could be relevant to human ALS pathobiology and disease treatment.
Journal ArticleDOI
Neonatal Hypoxia Ischaemia: Mechanisms, Models, and Therapeutic Challenges
TL;DR: Neonatal hypoxia-ischaemia is examined, evidence for the relevance of subplate-secreted molecules to this condition is reviewed, and Neuroserpin, a neuronally released neuroprotective factor, is discussed as a case study for developing new potential pharmacological interventions for use post- ischaemic injury.
Journal ArticleDOI
New horizons for newborn brain protection: enhancing endogenous neuroprotection
TL;DR: Remote ischaemic postconditioning whereby endogenous brain tolerance can be activated through hypoxia/reperfusion stimuli started immediately after the index hypoxic-ischaemic insult is discussed.
Journal ArticleDOI
The mechanisms and treatment of asphyxial encephalopathy.
TL;DR: The known mechanisms of hypoxic-ischemic brain injury in relation to the known effects of hypothermic neuroprotection are dissected.
Journal ArticleDOI
Mitochondria: hub of injury responses in the developing brain
TL;DR: A picture emerges in which mitochondrial biogenesis, mitophagy, migration, and morphogenesis are crucial for brain development and synaptic pruning, and play a part in recovery after acute insults.
References
More filters
Journal ArticleDOI
Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics.
TL;DR: Apoptosis seems to be involved in cell turnover in many healthy adult tissues and is responsible for focal elimination of cells during normal embryonic development, and participates in at least some types of therapeutically induced tumour regression.
Journal ArticleDOI
Cytochrome c and dATP-Dependent Formation of Apaf-1/Caspase-9 Complex Initiates an Apoptotic Protease Cascade
Peng Li,Deepak Nijhawan,Imawati Budihardjo,Srinivasa M. Srinivasula,Manzoor Ahmad,Emad S. Alnemri,Xiaodong Wang +6 more
TL;DR: Mutation of the active site of caspase-9 attenuated the activation of cazase-3 and cellular apoptotic response in vivo, indicating that casp enzyme-9 is the most upstream member of the apoptotic protease cascade that is triggered by cytochrome c and dATP.
Journal ArticleDOI
Induction of apoptotic program in cell-free extracts : requirement for datp and cytochrome c
TL;DR: Cells undergoing apoptosis in vivo showed increased release of cy tochrome c to their cytosol, suggesting that mitochondria may function in apoptosis by releasing cytochrome c.
Journal ArticleDOI
Cleavage of BID by Caspase 8 Mediates the Mitochondrial Damage in the Fas Pathway of Apoptosis
TL;DR: The results indicate that BID is a mediator of mitochondrial damage induced by Casp8, and coexpression of BclxL inhibits all the apoptotic changes induced by tBID.
Journal ArticleDOI
The Bcl2 family: regulators of the cellular life-or-death switch.
Suzanne Cory,Jerry M. Adams +1 more
TL;DR: A better understanding of how the Bcl2 family controls caspase activation should result in new, more effective therapeutic approaches in tissue homeostasis and cancer.