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Acute brain cytokine responses after global birth hypoxia in the rat
Author(s) -
Ashdown Helen,
Joita Silvia,
Luheshi Giamal N.,
Boksa Patricia
Publication year - 2008
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.21785
Subject(s) - hypoxia (environmental) , proinflammatory cytokine , asphyxia , brain damage , medicine , endocrinology , cytokine , neuroprotection , perinatal asphyxia , tumor necrosis factor alpha , central nervous system , inflammation , anesthesia , chemistry , organic chemistry , oxygen
The main cause of hypoxic/ischemic brain damage in term human neonates is intrauterine asphyxia, in which the whole body is subjected to hypoxia. Inflammatory cytokines are thought to play an important role in modulating hypoxic/ischemic damage in immature brain. Evidence for this from animal models is based mainly on studies that used a model of carotid artery ligation with hypoxia in postnatal rats. However, little is known about the role of cytokines in brain injury after whole‐body hypoxia at the time of birth. This study used a well‐established rat model of global birth hypoxia to assess mRNA and protein expression of three key proinflammatory cytokines, interleukin‐1β (IL‐1β), IL‐6, and tumor necrosis factor‐α, (TNF‐α) in the brain, liver, and kidney of neonates. We observed decreased IL‐1β and TNF‐α protein, and decreased IL‐6 mRNA in brains of neonates in the 2 hr after birth hypoxia but increased IL‐6 and IL‐1β in liver compared with vaginally born controls. Increasing the severity of the insult by increasing the period of anoxic exposure further decreased brain IL‐1β, whereas delivering anoxia under hypothermic conditions, known to be neuroprotective, attenuated the decrease in brain IL‐1β. These data suggest that decreased brain levels of inflammatory cytokines may modulate central nervous system responses to global birth hypoxia in rats. Our findings of decreased brain cytokine expression after global birth hypoxia contrast with reports of increased brain cytokines after carotid artery ligation with hypoxia in postnatal rats; possible reasons for these differences are discussed. © 2008 Wiley‐Liss, Inc.