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Objectives People with stroke sit for long periods each day, which may compromise blood glucose control and increase risk of recurrent stroke. Studies in other populations have found regular activity breaks have a significant immediate (within-day) positive effect on glucose metabolism. We examined the effects of breaking up uninterrupted sitting with frequent, short bouts of light-intensity physical activity in people with stroke on post-prandial plasma glucose and insulin. Methods Randomized within-participant crossover trial. We included people between 3 months and 10 years post-stroke, ambulant with minimal assistance and not taking diabetic medication other than metformin. The three experimental conditions (completed in random order) were: sitting for 8 h uninterrupted, sitting with 3 min bouts of light-intensity exercise while standing every 30 min, or sitting with 3 min of walking every 30 min. Meals were standardized and bloods were collected half- to one-hourly via an intravenous cannula. Results A total of 19 participants (9 female, mean [SD] age 68.2 [10.2]) completed the trial. The majority ( n = 12, 63%) had mild stroke symptoms (National Institutes of Stroke Scale score 0–13). There was no significant effect of experimental condition on glucose (mean [SD] positive incremental area [+iAUC] mmol·L·h-1 under the curve during sitting 42.3 [29.5], standing 47.4 [23.1], walking 44.6 [26.5], p = 0.563) or insulin (mean + iAUC pmol·L·h-1 sitting 14,161 [7,560], standing 14,043 [8,312], walking 14,008 [8,269], p = 0.987). Conclusion Frequent, short bouts of light-intensity physical activity did not have a significant effect on post-prandial plasma glucose and insulin in this sample of people with stroke. Further studies are needed to identify strategies that improve inactivity-related glucose metabolism after stroke.

Cerebral ischemia results in damage to neuronal circuits and lasting impairment in function. We have previously reported that stimulation of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors with the ampakine, CX1837, increases brain-derived neurotrophic factor (BDNF) levels and affords significant motor recovery after stroke in young mice. Here, we investigated whether administration of CX1837 in aged (24 months old) mice was equally effective. In a model of focal ischemia, administration of CX1837 from 5 days after stroke resulted in a small gain of motor function by week 6 after stroke. Mice that received a local delivery of BDNF via hydrogel implanted into the stroke cavity also showed a small gain of function from 4 to 6 weeks after stroke. Combining both treatments, however, resulted in a marked improvement in motor function from 2 weeks after insult. Assessment of peri-infarct tissue 2 weeks after stroke revealed a significant increase in p-AKT and p-CREB after the combined drug treatment. Using the pan-AKT inhibitor, GSK-690693, or deletion of CREB from forebrain neurons using the CREB-flox/CAMKii-cre mice, we were able to block the recovery of motor function. These data suggest that combined CX1837 and local delivery of BDNF are required to achieve maximal functional recovery after stroke in aged mice, and is occurring via the AKT-GSK3-CREB signaling pathway.

Excessive sitting is detrimentally associated with cardiovascular disease and all-cause mortality. Frequent breaks in prolonged sitting can improve cardiometabolic responses in non-stroke populations. However, this has not been established in stroke survivors. This study will determine the most effective dose of activity breaks that (i) produce clinically meaningful improvements in mean systolic blood pressure (primary outcome), postprandial glucose, and insulin responses (secondary outcomes), and (ii) is safe and feasible. We hypothesis that systolic blood pressure, postprandial insulin, and glucose responses will improve with increasing doses of activity and be most effective at the maximum safe and feasible dose of activity. Thirty participants in the most effective dose will provide 80% power to detect a within-person, between-condition, difference of 3.5 mmHg in systolic blood pressure assuming a SD of 15 mmHg, within-person correlation of 0.9, and α = 0.05. Stroke survivors will complete 3 experimental conditions in a within-participant, dose escalation design including (i) uninterrupted sitting (8 h), (ii) Dose 1: uninterrupted sitting with bouts of light-intensity exercises while standing (initial dose involves two 5-min breaks), and (iii) Dose 2: two additional 5-min breaks above Dose 1. Ambulatory blood pressure will be collected every 30 min during experimental conditions and hourly for 24-h post-experimental conditions. Blood samples will be collected every 30 min during 2-h postprandial periods. This study will identify the most effective dose of light-intensity exercises while standing to improve cardiometabolic responses in stroke survivors.

Exposure to social stress has been linked to the development and maintenance of mood-related psychopathology; however, the underlying neurobiological changes remain uncertain. In this study, we examined numbers of DFosB-immunoreactive cells in the forebrains of rats subjected to 12 episodes of social defeat. This was achieved using the social conflict model whereby animals are introduced into the home cage of older males (‘‘residents’’) trained to attack and defeat all such ‘‘intruders’’; importantly, controls were treated identically except that the resident was absent. Our results indicated that the only region in which DFosB-positive cells were found in significantly higher numbers in intruders than in controls was the infralimbic medial prefrontal cortex (mPFC). This same effect was not apparent using another psychological stressor, noise stress. Cells of the infralimbic mPFC also displayed evidence of chromatin remodeling. We found that exposure to repeated episodes of social defeat increased numbers of cells immunoreactive for histone H3 acetylation, but not for histone H3 phosphoacetylation, in the infralimbic mPFC. Collectively, these findings highlight the importance of the infralimbic mPFC in responding to social stress—a finding that provides insight into the possible neurobiological alterations associated with stress-induced psychiatric illness.

This article provides a brief commentary on Pfaff et al's timely review of the relations between mechanisms of CNS arousal and mechanisms of stress. Pfaff and colleagues use the review as a platform to propose the existence of a coherent stress-arousal state. We suggest that this proposal is, on a number of grounds, flawed. In turn, we counter that the while the states of stress and arousal are related they are as entities fundamentally separate. Moreover, we propose that any productive attempt to unite the two states must acknowledge the importance of and therefore centrally include higher order integrative phenomena, such as, appraisal.

Microglia are unique cells within the central nervous system because of their biophysical independence. As a result of this unusual property the cells must undergo significant structural remodelling in order to engage and connect with other elements within the central nervous system. Efficient remodelling is required for all activities that microglia are involved in ranging from monitoring synaptic information flow through to phagocytosis of tissue debris. Despite the fact that morphological remodelling is a pre-requisite to all microglial activities, relatively little research has been undertaken on the topic. This review examines what is known about how microglia transform themselves during development, under physiological conditions in response to changes in neuronal activity, and under pathological circumstances. Specific attention is given to exploring a variety of models that have been proposed to account for microglial transformation as well as the signals that are known to trigger these transformations.

Publisher Summary Emotions serve to facilitate decision making, and to organize and to motivate behavior. The advent of new techniques for investigating the structure and function of the brain, particularly the introduction of neuroimaging tools that allows one to study localized brain function during prescribed tasks, has led to a rapid improvement in the understanding of the neural substrates of emotional processing. The systems that have been put forward for describing emotions can be thought of as falling into two groups: categorical and dimensional. From a neurobiological perspective, the significance of these alternative approaches rests in the different ways in which they relate to associated theories concerning the neural underpinnings of emotion. Categorical systems are more numerous than dimensional systems and assume that there are a certain number of discrete, “basic” emotions; other emotions, if recognized, are seen as reflecting either differing levels of intensity. An alternative to a categorical system for describing emotions is a dimensional system. Although the categorical and dimensional systems are often characterized as constituting almostmutually exclusive alternatives, they can in some instances be regarded as complementary. Shifts in emotional state can be triggered by external or internal stimuli, with the latter category including thoughts, memories, or even one's conscious awareness of feelings generated by an antecedent emotion. Emotional appraisal can occur consciously or unconsciously, and studies on both human and non-human animals have provided strong evidence of a critical role for the amygdala in this process.