IL-4 mediates the delayed neurobehavioral impairments induced by neonatal hepatitis B vaccination that involves the down-regulation of the IL-4 receptor in the hippocampus

Xiao, Wang; Yang, Jiliang; Xing, Zhimin; Zhang, Hongyang; Wen, Yaru; Qi, Fangfang; Zuo, Zejie; Xu, Jie; Ye, Zhibin

doi:10.1016/j.cyto.2018.04.037

Cited by 12 publications

(14 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Interestingly, other experimental evidence suggests that elevated IL-4 levels demonstrated hippocampal neuroinflammation and cognitive decline in a mouse model. IL-4 also plays a crucial role in hepatitis B vaccinationinduced brain development and cognition [51].…”

Section: Discussionmentioning

confidence: 99%

Neuroinflammation trajectories precede cognitive impairment after experimental meningitis—evidence from an in vivo PET study

Giridharan

Collodel²,

Generoso³

et al. 2020

J Neuroinflammation

View full text Add to dashboard Cite

Background: Bacterial meningitis is a devastating central nervous system (CNS) infection with acute and long-term neurological consequences, including cognitive impairment. The aim of this study was to understand the association between activated microglia-induced neuroinflammation and post-meningitis cognitive impairment. Method: Meningitis was induced in male Wistar rats by injecting Streptococcus pneumoniae into the brain through the cisterna magna, and rats were then treated with ceftriaxone. Twenty-four hours and 10 days after meningitis induction, rats were imaged with positron emission tomography (PET) using [ 11 C]PBR28, a specific translocator protein (TSPO) radiotracer, to determine in vivo microglial activation. Following imaging, the expression of TSPO, cardiolipin, and cytochrome c, inflammatory mediators, oxidative stress markers, and glial activation markers were evaluated in the prefrontal cortex and hippocampus. Ten days after meningitis induction, animals were subjected to behavioral tests, such as the open-field, step-down inhibitory avoidance, and novel object recognition tests. Results: Both 24-h (acute) and 10-day (long-term) groups of rats demonstrated increased [ 11 C]PBR28 uptake and microglial activation in the whole brain compared to levels in the control group. Although free from infection, 10day group rats exhibited increased expression levels of cytokines and markers of oxidative stress, microglial activation (IBA-1), and astrocyte activation (GFAP) similar to those seen in the 24-h group. Acute meningitis induction also elevated TSPO, cytochrome c, and caspase-3 levels with no change in caspase-9 levels. Furthermore, upregulated levels of TSPO, cytochrome c, and caspase-3 and caspase-9 were observed in the rat hippocampus 10 days after meningitis induction with a simultaneous reduction in cardiolipin levels. Animals showed a cognitive decline in all tasks compared with the control group, and this impairment may be at least partially mediated by activating a glia-mediated immune response and upregulating TSPO. Conclusions: TSPO-PET could potentially be used as an imaging biomarker for microglial activation and long-term cognitive impairment post-meningitis. Additionally, this study opens a new avenue for the potential use of TSPO ligands after infection-induced neurological sequelae.

show abstract

Section: Discussionmentioning

confidence: 99%

Neuroinflammation trajectories precede cognitive impairment after experimental meningitis—evidence from an in vivo PET study

Giridharan

Collodel²,

Generoso³

et al. 2020

J Neuroinflammation

View full text Add to dashboard Cite

show abstract

“…While the underlying pathways through which vaccines provoke some neurobehavioural abnormalities in mice are still unclear, they seem to interfere with multiple neural and immune pathways during certain critical windows of nervous and immune system development, especially during the first two weeks of postnatal life when the brain-blood barrier is still immature and permeable [94].…”

Section: Discussionmentioning

confidence: 99%

Early postnatal injections of whole vaccines compared to placebo controls: Differential behavioural outcomes in mice

Eidi

Yoo

Bairwa

et al. 2020

Journal of Inorganic Biochemistry

View full text Add to dashboard Cite

“…There is a homeostasis between anti-inflammation and pro-inflammation in physiological condition, which plays an essential role in neural development and function. Elevated IL-4 levels due to any cause during the critical stages of brain development may break the physiological anti-inflammatory/pro-inflammatory balance in the brain, inducing strong immune activation and significantly increasing levels of pro-inflammatory cytokine which alter brain developmental trajectory and exert long-term effects on the brain (Wang et al 2018 ; Bilbo et al 2005 ). In addition, IL-4 may also contribute to brain damage via its ability to potentiate the effects of oxidative stress on neurons, and oxidative stress is one of the leading causes of inflammation in the central nervous systems (CNS) (Park et al 2008 ).…”

Section: Introductionmentioning

confidence: 99%

“…Kordulewska NK et al reported that children with autism showed an enhanced immune response and abnormal expression of cytokines, and the level of IL-4 was significantly increased than that in the control group, based on a comparison of blood samples from autistic patients and control participants (Kordulewska et al 2019 ). An animal experimental study also shown that peripheral IL-4 penetrated the blood–brain barrier (BBB) into the CNS during neonatal period, inducing delayed hippocampal neuroinflammation and spatial cognitive impairment through down-regulation of the IL-4 receptor in the hippocampus (Wang et al 2018 ).…”

Section: Introductionmentioning

confidence: 99%

Neonatal IL-4 Over-Exposure is Accompanied by Macrophage Accumulation in Dura Mater After Instant Anti-inflammatory Cytokine Response in CSF

Wang,

Sha,

et al. 2024

Cell Mol Neurobiol

Self Cite

View full text Add to dashboard Cite

Multiple studies have shown that clinical events resulting into neonatal IL-4 over-exposure, such as asthma in early life and food allergy, were associated with brain damage and that the neuroinflammation induced by them might lead to cognitive impairments, anxiety-/depressive-like behaviors. IL-4 is the most major elevated cytokine in periphery when these clinical events occur and peripheral IL-4 level positively correlates with the severity of those events. Our previous studies have verified that neonatal IL-4 over-exposure induced a delayed neuroinflammatory damage in rodents, which might have adverse implications for brain development and cognition. Neuroinflammation in brain parenchyma is often accompanied by changes in CSF cytokines levels. However, whether the cytokines levels in CSF change after neonatal IL-4 over-exposure is unknown. Here, we found a delayed pro-inflammatory cytokines response (higher IL-6, IL-1β and, TNF levels) in both hippocampus and CSF after an instant anti-inflammatory cytokine response in IL-4 over-exposed rats. Moreover, the pro-inflammatory cytokines response appeared earlier in CSF than in hippocampus. The level of each of the pro-inflammatory cytokines in CSF positively correlated with that in hippocampus at the age of postnatal day 42. More microglia numbers/activation and higher M-CSF level in the hippocampus in IL-4 over-exposed rats were also observed. Furthermore, there were more macrophages with inflammatory activation in dural mater of IL-4 over-exposed rats. In sum, neonatal IL-4 over-exposure in rats induces delayed inflammation in CSF, suggesting CSF examination may serve as a potential method in predicting delayed neuroinflammation in brain following neonatal IL-4 over-exposure. Graphical Abstract

show abstract

IL-4 mediates the delayed neurobehavioral impairments induced by neonatal hepatitis B vaccination that involves the down-regulation of the IL-4 receptor in the hippocampus

Cited by 12 publications

References 34 publications

Neuroinflammation trajectories precede cognitive impairment after experimental meningitis—evidence from an in vivo PET study

Neuroinflammation trajectories precede cognitive impairment after experimental meningitis—evidence from an in vivo PET study

Early postnatal injections of whole vaccines compared to placebo controls: Differential behavioural outcomes in mice

Neonatal IL-4 Over-Exposure is Accompanied by Macrophage Accumulation in Dura Mater After Instant Anti-inflammatory Cytokine Response in CSF

Contact Info

Product

Resources

About