Pictured above is a graphical abstract from the article "Neutralizing anti-interleukin-1β antibodies reduce ischemia-related interleukin-1β transport across the blood–brain barrier in fetal sheep" by Aparna Patra, Xiaodi Chen, Grazyna B. Sadowska, Jiyong Zhang, Yow-Pin Lim, James F. Padbury, William A. Banks and Barbara S. Stonestreet.
The journal features papers describing the results of original research on any aspect of the scientific study of the nervous system. Any paper, however short, is considered for publication provided that it reports significant, new and carefully confirmed findings with full experimental details.
READ the current issue of IBRO Neuroscience (vol. 346) published on 27 March 2017.
Highlights from this issue include:
(Gustavo Scola, Angela Duong)
Growing evidence from epidemiological studies strongly suggests maternal infection as a risk factor for psychiatric disorders including bipolar disorder, schizophrenia, and autism. Animal studies support this association and demonstrate that maternal immune activation (MIA) changes brain morphology and inflammatory cytokines in the adult offspring. Evidence for changes in inflammatory cytokines is also demonstrated in human post-mortem brain and peripheral blood studies from subjects with psychiatric disorders. This perspective briefly highlights convincing evidence from epidemiological, preclinical and human pathological studies to support the role of MIA in major psychiatric disorders. A better understanding of the link between MIA and brain development in psychiatric disorders will lead to the development of novel immunomodulatory interventions for individuals at risk for psychiatric disorders.
(Qiushi Zhang, Xueqian Yang, Li Yao, Xiaojie Zhao)
Working memory (WM) refers to the holding and manipulation of information during cognitive tasks. Its underlying neural mechanisms have been explored through both functional magnetic resonance imaging (fMRI) and electroencephalography (EEG). Trial-by-trial coupling of simultaneously collected EEG and fMRI signals has become an important and promising approach to study the spatio-temporal dynamics of such cognitive processes. Previous studies have demonstrated a modulation effect of the WM load on both the BOLD response in certain brain areas and the amplitude of P3. However, much remains to be explored regarding the WM load-dependent relationship between the amplitude of ERP components and cortical activities, and the low signal-to-noise ratio (SNR) of the EEG signal still poses a challenge to performing single-trial analyses. In this paper, we investigated the spatio-temporal activities of P3 during an n-back verbal WM task by introducing an adaptive wavelet denoiser into the extraction of single-trial P3 features and using general linear model (GLM) to integrate simultaneously collected EEG and fMRI data. Our results replicated the modulation effect of the WM load on the P3 amplitude. Additionally, the activation of single-trial P3 amplitudes was detected in multiple brain regions, including the insula, the cuneus, the lingual gyrus (LG), and the middle occipital gyrus (MOG). Moreover, we found significant correlations between P3 features and behavioral performance. These findings suggest that the single-trial integration of simultaneous EEG and fMRI signals may provide new insights into classical cognitive functions.
(Aparna Patra, Xiaodi Chen, Grazyna B. Sadowska, Jiyong Zhang, Yow-Pin Lim, James F. Padbury, William A. Banks, Barbara S. Stonestreet)
Hypoxic ischemic insults predispose to perinatal brain injury. Pro-inflammatory cytokines are important in the evolution of this injury. Interleukin-1β (IL-1β) is a key mediator of inflammatory responses and elevated IL-1β levels in brain correlate with adverse neurodevelopmental outcomes after brain injury. Impaired blood–brain barrier (BBB) function represents an important component of hypoxic-ischemic brain injury in the fetus. In addition, ischemia–reperfusion increases cytokine transport across the BBB of the ovine fetus. Reducing pro-inflammatory cytokine entry into brain could represent a novel approach to attenuate ischemia-related brain injury. We hypothesized that infusions of neutralizing IL-1β monoclonal antibody (mAb) reduce IL-1β transport across the BBB after ischemia in the fetus. Fetal sheep were studied 24-h after 30-min of carotid artery occlusion. Fetuses were treated with placebo- or anti-IL-1β mAb intravenously 15-min and 4-h after ischemia. Ovine IL-1β protein expressed from IL-1β pGEX-2T vectors in Escherichia coli (E. coli) BL-21 cells was produced, purified, and radiolabeled with 125I. BBB permeability was quantified using the blood-to-brain transfer constant (Ki) with 125I-radiolabeled-IL-1β. Increases in anti-IL-1β mAb were observed in the brain of the mAb-treated group (P < 0.001). Blood-to-brain transport of 125I-IL-1β was lower (P < 0.04) across brain regions in the anti-IL-1β mAb-treated than placebo-treated ischemic fetuses. Plasma 125I-IL-1β counts were higher (P < 0.001) in the anti-IL-1β mAb- than placebo-treated ischemic fetuses. Systemic infusions of anti-IL-1β mAb reduce IL-1β transport across the BBB after ischemia in the ovine fetus. Our findings suggest that conditions associated with increases in systemic pro-inflammatory cytokines and neurodevelopmental impairment could benefit from an anti-cytokine therapeutic strategy.
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