The biology and pathology of hypoxia-ischemia: an update.
After an hypoxic-ischemic (HI) insult, a multi-faceted complex cascade of events occurs that ultimately causes cell death and neurological damage to the central nervous system. The various cascades include, amongst others: immunological changes, such as the activation of the complement system and the generation of antibodies; increased inflammation through the actions of pro-inflammatory cytokines and chemokines; the production of reactive oxygen species leading to oxidative stress; and diminished mitochondrial function leading to the activation of apoptotic pathways and subsequent alteration in the function of neurons within the contralateral hemisphere. This review addresses the immunological aspects following HI, the role of various cytokines (both pro-inflammatory and anti-inflammatory) and chemokines after the induction of HI. In addition, the role of free radicals in producing HI-induced neurodegeneration and the contribution that mitochondrial dysfunction has in neuronal apoptotic cell death will be discussed. This review also covers the changes that the previously assumed "internal control", the contralateral hemisphere, undergoes due to HI and describes the difficulties associated with therapy intended to prevent neuronal injury associated with HI.
Department of Pharmacology and Toxicology, University of Otago, Dunedin, New Zealand.
Andrew N
AN
Clarkson
Brad A
BA
Sutherland
Ian
I
Appleton
D000818:Animals; D016923:Cell Death; D002490:Central Nervous System / Q000473:pathology; D018925:Chemokines / Q000378:metabolism; D003167:Complement Activation; D016207:Cytokines / Q000378:metabolism; D005609:Free Radicals; D006801:Humans; D000860:Hypoxia; D020925:Hypoxia-Ischemia, Brain / Q000473:pathology*; D007107:Immune System; D007249:Inflammation; D007511:Ischemia; D008928:Mitochondria / Q000473:pathology; D009389:Neovascularization, Pathologic; D019636:Neurodegenerative Diseases / Q000473:pathology; D009474:Neurons / Q000378:metabolism; D018384:Oxidative Stress; D017382:Reactive Oxygen Species
D018925:Chemokines; D016207:Cytokines; D005609:Free Radicals; D017382:Reactive Oxygen Species