Neuroscience
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Heightened concentrations of CO2 in inhaled air provoke temporary acidification of the brain, followed by compensatory hyperventilation and increased arousal/anxiety. These responses are likely to map a basic, latent general alarm/avoidance system that is largely shared across mammals, and are sources of individual differences. By showing paroxysmal respiratory and emotional responses to CO2 challenges, humans with panic and separation anxiety disorders lie at one extreme of the distribution for CO2 sensitivity. ⋯ Advantages of modeling CO2 sensitivity in rodents include non-inferential measurements (e.g. respiratory readouts) as proxies for human conditions, unbiased investigation of gene-environment interplays, and flexible availability of tissues for mechanistic studies. Data in humans and animals such as those reported in this issue of Neuroscience begin to reveal that CO2-driven behavioral responses stem from anatomo-physiological systems that are relatively separated from those subserving general dispositions to anxiety. This supports the notion that sensitivity to suffocative stimuli and ensuing human panic are significantly independent from trait/cognitive anxiety, and corroborates newer conceptualizations that distinguish between fear and anxiety circuitries.
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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. ⋯ 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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Spinal cord stimulation (SCS) has been suggested as a therapeutic technique for treating patients with disorder of consciousness (DOC). Although studies have reported its benefits for patients, the underlying pathophysiological mechanisms remain unclear. The aim of this study was to measure the effects of SCS on the EEG of patients in a minimally conscious state (MCS), which would allow us to explore the possible workings underpinning of the approach. ⋯ The main findings of this study were that: (1) significantly altered relative power and synchronisation was found in delta and gamma bands after one SCS stimulation using 5Hz, 70Hz or 100Hz; (2) bicoherence showed that coupling within delta was significantly decreased after stimulation using 70Hz, while reduction of coupling between delta and gamma was found when using 5Hz and 100Hz. However, SCS of 20Hz, 50Hz and sham stimulation did not induce changes in any frequency band at any region. This study showed EEG evidence that SCS can modulate the brain function of MCS patients, speculatively by activating the formation-thalamus-cortex network.
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Inhalation of carbon dioxide (CO2) is frequently employed as a biological challenge to evoke intense fear and anxiety. In individuals with panic disorder, CO2 reliably evokes panic attacks. Sensitivity to CO2 is highly heterogeneous among individuals, and although a genetic component is implicated, underlying mechanisms are not clear. ⋯ Conversely, DβH-positive cell counts within the LC were significantly higher in CO2-sensitive strains. Collectively, our data provide evidence for strain dependent, differential CO2-sensitivity and potential differences in monoaminergic systems regulating panic and anxiety. Comparative studies between CO2-vulnerable and resistant strains may facilitate the mechanistic understanding of differential CO2-sensitivity in the development of panic and anxiety disorders.
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Diabetes mellitus (DM) is associated with cognitive deficits and an increased risk of Alzheimer's disease (AD). Recently, a newly identified heptapeptide of the renin-angiotensin system (RAS), angiotensin-(1-7) [Ang-(1-7)], was found to protect against brain damage. This study investigated the effects of Ang-(1-7) on diabetes-induced cognitive deficits. ⋯ These protective effects were significantly reversed by the co-administration of A779. These findings show that Ang-(1-7) is a promising therapeutic target for diabetes-induced cognitive impairment. The neuroprotective effects of Ang-(1-7) were mainly through Mas receptor (MasR) activation.