Acute brain cytokine responses after global birth hypoxia in the rat

Ashdown, Helen; Joiţa, Silvia; Luheshi, Giamal N.; Boksa, Patricia

doi:10.1002/jnr.21785

Cited by 17 publications

(28 citation statements)

References 56 publications

(74 reference statements)

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“…Secondly, a decrease of pro-inflammatory cytokines can follow hypoxia in newborn rats (Ashdown et al 2008). This is consistent with decreasing TNF-a with birth problems and a trend for decreasing IFN-c with poor APGAR indices of oxygenation in the present study.…”

Section: Birthsupporting

confidence: 88%

An exploration of the associations of pregnancy and perinatal features with cytokines and tryptophan/kynurenine metabolism in children with attention-deficit hyperactivity disorder (ADHD)

Oades

2011

ADHD Atten Def Hyp Disord

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Intra-individual variability of the characteristics of children with attention-deficit hyperactivity (ADHD) may reflect compromised glial energy supply in the synapse. We reported recently that while serum levels of a glial marker, the cytokine S100B, were not seriously altered, levels of other cytokines and tryptophan metabolites were related to symptoms, attention and variability. Here, we explore with a regression analysis whether levels of these substances were associated with features of the index pregnancy of potential aetiological significance. Serum was taken from 35 children with DSM-IV ADHD (14 on medication) and 21 typically developing controls to measure 8 cytokines (S100B, IL-2, IL-6, IL-10, IL-13, IL-16, TNF-α and IFN-γ) and 5 metabolites (Tryptophan, Kynurenine, Kynurenate [KA], 3-hydroxy-kynurenine [3HK] and 5-hydroxyindole acetic acid [5-HIAA]). The mothers received a 124-item questionnaire on features surrounding the pregnancy. (1) For children with ADHD, a shorter pregnancy and smaller birth weight were associated statistically with increased 3HK and IFN-γ and for obstetric problems with decreased TNF-α levels. (2) Maternal smoking related to decreasing kynurenine and increasing 3HK and S100B levels in ADHD children. Paternal smoking was associated with increased tryptophan in the controls and increased IL-6 levels in ADHD children. (3) The taking of supplements often related to decreasing TNF-α, increasing IL-10 and lower 5-HIAA levels in the ADHD children. Less 5-HIAA but more tryptophan was associated with earlier and later life events, respectively. (4) Increased IL-16 and 5-HIAA levels in the ADHD group related to reports of poorer infant health. Unexpectedly, more child care (seafood and time together) in ADHD than healthy families was implicated by lower tryptophan levels and an altered balance of pro-inflammatory cytokines. Across measures control families generally showed either non-significant associations or the opposite to those of the ADHD group. In ADHD children more than controls, the balance of potentially toxic or protective kynurenine metabolites and of pro- over anti-inflammatory cytokines may reflect the perinatal experience associated with stress, but not with maternal illness.

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Section: Birthsupporting

confidence: 88%

An exploration of the associations of pregnancy and perinatal features with cytokines and tryptophan/kynurenine metabolism in children with attention-deficit hyperactivity disorder (ADHD)

Oades

2011

ADHD Atten Def Hyp Disord

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“…The increase in cytokine mRNA levels observed acutely after FA is not surprising. Many studies have highlighted that asphyxia induces inflammatory responses [6, 12, 14, 15]. It seems that in our study, the cerebellum can cope with the inflammation and is able to attenuate this response later on since the inflammatory cytokine responses are decreased at 96 h post-FA.…”

Section: Discussionsupporting

confidence: 49%

Cerebellar Cytokine Expression in a Rat Model for Fetal Asphyctic Preconditioning and Perinatal Asphyxia

et al. 2014

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Asphyctic brain injury is a major cause of neuronal inflammation in the perinatal period. Fetal asphyctic preconditioning has been shown to modulate the cerebral inflammatory cytokine response, hereby protecting the brain against asphyctic injury at birth. This study was designated to examine the effects of perinatal asphyxia and fetal asphyctic preconditioning on the inflammatory cytokine response in the cerebellum. Fetal asphyxia was induced at embryonic day 17 by clamping the uterine vasculature for 30 min. At term birth, global perinatal asphyxia was induced by placing the uterine horns in saline for 19 min. Pro- and anti-inflammatory cytokine expression were assessed by real-time PCR and immunohistochemistry in cerebella of newborn rats. We found that tumor necrosis factor alpha and interleukin-10 mRNA were increased 12 h after fetal asphyxia, while the inflammatory cytokine response was decreased 96 h postfetal asphyxia. When applied as preconditioning stimulus, fetal asphyxia attenuates the cerebellar cytokine response. These results indicate that sublethal fetal asphyxia may protect the cerebellum from perinatal asphyxia-induced damage via inhibition of inflammation.

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“…For instance, Ashdown et al [43] described an increase in hepatic IL-1β and IL-6 protein levels following 15 min of global hypoxia in a neonatal rat model. Furthermore, several studies show that hypoxic conditions induce activation of several transcriptional pathways including HIF-1α, NF-κB and JNK, which together regulate the transcription of more than 100 genes involved in inflammation [44,45,46,47,48].…”

Section: Discussionmentioning

confidence: 99%

Cerebral and Hepatic Inflammatory Response after Neonatal Hypoxia-Ischemia in Newborn Rats

Bonestroo¹,

Nijboer²,

Velthoven³

et al. 2013

Dev Neurosci

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Background: Neonatal encephalopathy induced by perinatal asphyxia is a serious condition associated with high mortality and morbidity. Inflammation after the insult is thought to contribute to brain injury. This inflammatory response to hypoxia-ischemia (HI) may not only occur in the brain but also in peripheral organs. The aim of the present study was to investigate the effect of neonatal HI on the inflammatory response in the liver in comparison to inflammation in the brain. Methods: HI was induced in P7 Wistar rats by unilateral carotid artery occlusion and hypoxia. Cytokine and chemokine mRNA levels were determined in the brain and liver by quantitative PCR. Polarization of brain macrophages to the M1/M2-like phenotype and infiltration of neutrophils were characterized by immunohistochemistry. Results: 3 h after HI, an upregulation of the proinflammatory cytokines TNF-α and IL-1β and anti-inflammatory IL-10 was observed in the ipsilateral hemisphere of the brain compared to mRNA levels in sham-operated animals. Additionally, cerebral CINC-1 and MCP-1 mRNA expressions were increased. We also observed increased numbers of macrophages/microglia of the M1-like phenotype as well as a small increase in granulocyte influx in the ipsilateral hemisphere. Conversely, in the liver 3 h after HI, a downregulation of TNF-α, IL-1β, and MCP-1 and a trend towards an upregulation of IL-10 were observed compared to mRNA levels of sham-operated animals. However, hepatic CINC-1 expression was increased compared to levels in sham-operated animals. Following systemic hypoxia only, no significant changes in the expression of TNF-α, CINC-1 or MCP-1 were observed in the liver compared to sham-operated littermates, except for an upregulation in hepatic IL-1β expression 3 h after hypoxia. Twenty-four hours after insult, cerebral ipsilateral TNF-α, MCP-1 and CINC-1 mRNA expression was still increased, together with an increase in TGF-β expression. Moreover, an increase in macrophages/microglia of the M1-like phenotype was observed together with the appearance of macrophages/microglia of the M2-like phenotype around the cerebral lesion as well as an increase in granulocyte influx in comparison to 3 h after HI. In the liver, 24 h after HI, cytokine and chemokine responses were similar to mRNA levels in sham-operated animals except for a decrease in IL-10 and MCP-1. Conclusion: We describe for the first time that brain damage following neonatal HI induces an early downregulation of the proinflammatory response in the liver. HI induces an early proinflammatory response in the brain with a concomitant increase in influx of neutrophils and polarization of macrophages/microglia to the M1-like phenotype starting at 3 h and increasing up to 24 h after HI. The inflammatory state of the brain changes after 24 h, with an increase in the anti-inflammatory cytokine TGF-β together with the appearance of macrophages/microglia of the M2-like phenotype. The downregulation of proinflammatory cytokines in the liver is not due to systemic hypoxia only, but i...

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Acute brain cytokine responses after global birth hypoxia in the rat

Cited by 17 publications

References 56 publications

An exploration of the associations of pregnancy and perinatal features with cytokines and tryptophan/kynurenine metabolism in children with attention-deficit hyperactivity disorder (ADHD)

An exploration of the associations of pregnancy and perinatal features with cytokines and tryptophan/kynurenine metabolism in children with attention-deficit hyperactivity disorder (ADHD)

Cerebellar Cytokine Expression in a Rat Model for Fetal Asphyctic Preconditioning and Perinatal Asphyxia

Cerebral and Hepatic Inflammatory Response after Neonatal Hypoxia-Ischemia in Newborn Rats

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