Objective This experiment tested the hypothesis that exercise would improve executive function. Design Sedentary, overweight 7- to 11-year-old children (N = 171, 56% female, 61% Black, M ± SD age 9.3 ± 1.0 yrs, body mass index (BMI) 26 ± 4.6 kg/m2, BMI z-score 2.1 ± 0.4) were randomized to 13 ± 1.6 weeks of an exercise program (20 or 40 minutes/day), or a control condition. Main outcome measures Blinded, standardized psychological evaluations (Cognitive Assessment System and Woodcock-Johnson Tests of Achievement III) assessed cognition and academic achievement. Functional magnetic resonance imaging measured brain activity during executive function tasks. Results Intent to treat analysis revealed dose response benefits of exercise on executive function and mathematics achievement. Preliminary evidence of increased bilateral prefrontal cortex activity and reduced bilateral posterior parietal cortex activity due to exercise was also observed. Conclusion Consistent with results obtained in older adults, a specific improvement on executive function and brain activation changes due to exercise were observed. The cognitive and achievement results add evidence of dose response, and extend experimental evidence into childhood. This study provides information on an educational outcome. Besides its importance for maintaining weight and reducing health risks during a childhood obesity epidemic, physical activity may prove to be a simple, important method of enhancing aspects of children’s mental functioning that are central to cognitive development. This information may persuade educators to implement vigorous physical activity.

Traumatic brain injury (TBI) is a major cause of mortality and morbidity worldwide. Cerebral edema, a life-threatening medical complication, contributes to elevated intracranial pressure (ICP) and a poor clinical prognosis after TBI. Unfortunately, treatment options to reduce post-traumatic edema remain suboptimal, due in part, to a dearth of viable therapeutic targets. Herein, we tested the hypothesis that cerebral innate immune responses contribute to edema development after TBI. Our results demonstrate that high-mobility group box protein 1 (HMGB1) was released from necrotic neurons via a NR2B-mediated mechanism. HMGB1 was clinically associated with elevated ICP in patients and functionally promoted cerebral edema after TBI in mice. The detrimental effects of HMGB1 were mediated, at least in part, via activation of microglial toll-like receptor-4 (TLR4) and the subsequent expression of the astrocytic water channel, aquaporin-4 (AQP4). Genetic or pharmacological (VGX-1027) TLR4 inhibition attenuated the neuroinflammatory response and limited post-traumatic edema with a delayed, clinically implementable therapeutic window. Human and rodent tissue culture studies further defined the cellular mechanisms demonstrating neuronal HMGB1 initiates the microglial release of interleukin-6 (IL-6) in a TLR4 dependent mechanism. In turn, microglial IL-6 increased the astrocytic expression of AQP4. Taken together, these data implicate microglia as key mediators of post-traumatic brain edema and suggest HMGB1-TLR4 signaling promotes neurovascular dysfunction after TBI.

We report on abundance measurements of 10Be, 26Al, 36Cl, and 54Mn in the Galactic cosmic rays (GCRs) using the Cosmic-Ray Isotope Spectrometer (CRIS) instrument aboard the Advanced Composition Explorer spacecraft at energies from D70 to D400 MeV nucleon~1. We also report an upper limit on the abundance of GCR 14C. The high statistical signiÐcance of these measurements allows the energy dependence of their relative abundances to be studied. A steady-state, leaky-box propagation model, incorporating observations of the local interstellar medium (ISM) composition and density and recent partial fragmentation cross section measurements, is used to interpret these abundances. Using this model, the individual galactic conÐnement times derived using data for each species are consistent with a unique conÐnement time value of Myr. The CRIS abundance measurements are consis-q esc \ 15.0^1.6 tent with propagation through an average ISM hydrogen number density H atoms n H \ 0.34^0.04 cm~3. The surviving fractions, f, for each radioactive species have been calculated. From predictions of the di †usion models of Ptuskin & Soutoul, the values of f indicate an interstellar cosmic-ray di †usion coefficient of D \ (3.5^2.0) ] 1028 cm2 s~1.

Objective Children who are less fit reportedly have lower performance on tests of cognitive control and differences in brain function. This study examined the effect of an exercise intervention on brain function during two cognitive control tasks in overweight children. Design and Methods Participants included 43 unfit, overweight (BMI ≥ 85th percentile) children 8- to 11-years old (91% Black), who were randomly divided into either an aerobic exercise (n = 24) or attention control group (n = 19). Each group was offered a separate instructor-led after-school program every school day for 8 months. Before and after the program, all children performed two cognitive control tasks during functional magnetic resonance imaging (fMRI): antisaccade and flanker. Results Compared to the control group, the exercise group decreased activation in several regions supporting antisaccade performance, including precentral gyrus and posterior parietal cortex, and increased activation in several regions supporting flanker performance, including anterior cingulate and superior frontal gyrus. Conclusions Exercise may differentially impact these two task conditions, or the paradigms in which cognitive control tasks were presented may be sensitive to distinct types of brain activation that show different effects of exercise. In sum, exercise appears to alter efficiency or flexible modulation of neural circuitry supporting cognitive control in overweight children.

No abstract

In childhood, excess adiposity and low fitness are linked to poor academic performance, lower cognitive function, and differences in brain structure. Identifying ways to mitigate obesity-related alterations is of current clinical importance. This study examined the effects of an 8-month exercise intervention on the uncinate fasciculus, a white matter fiber tract connecting frontal and temporal lobes. Participants consisted of 18 unfit, overweight 8–11 year-old children (94% Black) who were randomly assigned to either an aerobic exercise (n=10) or a sedentary control group (n=8). Before and after the intervention, all subjects participated in a diffusion tensor MRI scan. Tractography was conducted to isolate the uncinate fasciculus. The exercise group showed improved white matter integrity as compared to the control group. These findings are consistent with an emerging literature suggesting beneficial effects of exercise on white matter integrity.

We report improved measurements of elemental abundances and spectra for galactic cosmic-ray (GCR) nuclei obtained by the Cosmic Ray Isotope Spectrometer on board NASA's Advanced Composition Explorer (ACE) spacecraft during the minimum and maximum phases of solar cycle 23. We discuss results for particles with nuclear charge 5 Z 28 and typical energies between 50 and 500 MeV nucleon −1. We demonstrate that a detailed "leaky box" Galactic propagation model combined with a spherically symmetric solar modulation model gives a good (but not perfect) fit to the observed spectra by using a solar modulation parameter of φ = 325 MV at solar minimum and φ = 900 MV at solar maximum. Although our results are generally consistent with previous measurements from space-based and balloon-based missions, there are significant differences. The large geometrical acceptance and excellent charge resolution of the instrument result in the most detailed and statistically significant record of GCR composition to date in this energy range. The measurements reported here serve as a high-precision baseline for continued studies of GCR composition, solar modulation over the solar cycle, space radiation hazards, and other applications.

Traumatic brain injury (TBI) is a leading cause of death and disability worldwide. Cerebral edema, the abnormal accumulation of fluid within the brain parenchyma, contributes to elevated intracranial pressure (ICP) and is a common life-threatening neurological complication following TBI. Unfortunately, neurosurgical approaches to alleviate increased ICP remain controversial and medical therapies are lacking due in part to the absence of viable drug targets. In the present study, genetic inhibition (P2X7−/− mice) of the purinergic P2x7 receptor attenuated the expression of the pro-inflammatory cytokine, interleukin-1β (IL-1β) and reduced cerebral edema following controlled cortical impact, as compared to wild-type mice. Similarly, brilliant blue G (BBG), a clinically non-toxic P2X7 inhibitor, inhibited IL-1β expression, limited edemic development, and improved neurobehavioral outcomes after TBI. The beneficial effects of BBG followed either prophylactic administration via the drinking water for one week prior to injury or via an intravenous bolus administration up to four hours after TBI, suggesting a clinically-implementable therapeutic window. Notably, P2X7 localized within astrocytic end feet and administration of BBG decreased the expression of glial fibrillary acidic protein (GFAP), a reactive astrocyte marker, and attenuated the expression of aquaporin-4 (AQP4), an astrocytic water channel that promotes cellular edema. Together, these data implicate P2X7 as a novel therapeutic target to prevent secondary neurological injury after TBI, a finding that warrants further investigation.