99mTc-HMPAO SPECT imaging reveals brain hypoperfusion during status epilepticus

Status epilepticus (SE) is a clinical emergency with high mortality. SE can trigger neuronal death or injury and alteration of neuronal networks resulting in long-term cognitive decline or epilepsy. Among the multiple factors contributing to this damage, imbalance between oxygen and glucose requirements and brain perfusion during SE has been proposed. Herein, we aimed to quantify by neuroimaging the spatiotemporal course of brain perfusion during and after lithium-pilocarpine-induced SE in rats. To this purpose, animals underwent 99mTc-HMPAO SPECT imaging at different time points during and after SE using a small animal SPECT/CT system. 99mTc-HMPAO regional uptake was normalized to the injected dose. In addition, voxel-based statistical parametric mapping was performed. SPECT imaging showed an increase of cortical perfusion before clinical seizure activity onset followed by regional hypo-perfusion starting with the first convulsive seizure and during SE. Twenty-four hours after SE, brain 99mTc-HMPAO uptake was widely decreased. Finally, chronic epileptic animals showed regionally decreased perfusion affecting hippocampus and cortical sub-regions. Despite elevated energy and oxygen requirements, brain hypo-perfusion is present during SE. Our results suggest that insufficient compensation of required blood flow might contribute to neuronal damage and neuroinflammation, and ultimately to chronic epilepsy generated by SE.

Feasibility and Reliability Assessment of Video-Based Motion Analysis and Surface Electromyography in Children with Fragile X during Gait

Fragile X Syndrome (FXS), the leading form of inherited intellectual disability and autism, is characterized by specific musculoskeletal conditions. We hypothesized that gait analysis in FXS could be relevant for the evaluation of motor control of gait, and help the understanding of a possible correlation between functional and intellectual abilities. Typical deficits in executive control and hyperactivity have hampered the use of standard gait analysis. The aim of our study was to quantitatively assess musculoskeletal alterations in FXS children in standard ambulatory conditions, in a friendly environment. Ten FXS children and sixteen controls, with typical neurodevelopment, were evaluated through four synchronized video cameras and surface electromyography; lower limb joints rotations, spatiotemporal parameters, duration of muscle contraction, activation timing and envelope peaks were determined. Reliability and repeatability of the video based kinematics analysis was assessed with respect to stereophotogrammetry. The Kruskal–Wallis Test (p < 0.05) or SPM1D were used to compare different groups of subjects. Results show a consistently altered gait pattern associated with abnormal muscle activity in FXS subjects: reduced knee and excessive hip and ankle flexion, and altered duration and activity onset on all the recorded muscles (Rectus/Biceps Femoris, Tibialis Anterior, Gastrocnemius Lateralis). Results of this study could help with planning personalized rehabilitations.

The darkness and the light: diurnal rodent models for seasonal affective disorder

ABSTRACTThe development of animal models is a critical step for exploring the underlying pathophysiological mechanisms of major affective disorders and for evaluating potential therapeutic approaches. Although most neuropsychiatric research is performed on nocturnal rodents, differences in how diurnal and nocturnal animals respond to changing photoperiods, combined with a possible link between circadian rhythm disruption and affective disorders, has led to a call for the development of diurnal animal models. The need for diurnal models is most clear for seasonal affective disorder (SAD), a widespread recurrent depressive disorder that is linked to exposure to short photoperiods. Here, we briefly review what is known regarding the etiology of SAD and then examine progress in developing appropriate diurnal rodent models. Although circadian disruption is often invoked as a key contributor to SAD, a mechanistic understanding of how misalignment between endogenous circadian physiology and daily environmental rhythms affects mood is lacking. Diurnal rodents show promise as models of SAD, as changes in affective-like behaviors are induced in response to short photoperiods or dim-light conditions, and symptoms can be ameliorated by brief exposure to intervals of bright light coincident with activity onset. One exciting avenue of research involves the orexinergic system, which regulates functions that are disturbed in SAD, including sleep cycles, the reward system, feeding behavior, monoaminergic neurotransmission and hippocampal neurogenesis. However, although diurnal models make intuitive sense for the study of SAD and are more likely to mimic circadian disruption, their utility is currently hampered by a lack of genomic resources needed for the molecular interrogation of potential mechanisms.

Microcircuit synchronization and heavy tailed synaptic weight distribution in preBötzinger Complex contribute to generation of breathing rhythm

The preBötzinger Complex, the mammalian inspiratory rhythm generator, encodes inspiratory time as motor pattern. Spike synchronization throughout this sparsely connected network generates inspiratory bursts albeit with variable latencies after preinspiratory activity onset in each breathing cycle. Using preBötC rhythmogenic microcircuit minimal models, we examined the variability in probability and latency to burst, mimicking experiments. Among various physiologically plausible graphs of 1000 point neurons with experimentally determined neuronal and synaptic parameters, directed Erdős-Rényi graphs best captured the experimentally observed dynamics. Mechanistically, preBötC (de)synchronization and oscillatory dynamics are regulated by the efferent connectivity of spiking neurons that gates the amplification of modest preinspiratory activity through input convergence. Furthermore, to replicate experiments, a lognormal distribution of synaptic weights was necessary to augment the efficacy of convergent coincident inputs. These mechanisms enable exceptionally robust yet flexible preBötC attractor dynamics that, we postulate, represent universal temporal-processing and decision-making computational motifs throughout the brain.

Entrainment of circadian rhythms of locomotor activity by ambient temperature cycles in the dromedary camel

In the dromedary camel, a well-adapted desert mammal, daily ambient temperature (Ta)-cycles have been shown to synchronize the central circadian clock. Such entrainment has been demonstrated by examining two circadian outputs, body temperature and melatonin rhythms. Locomotor activity (LA), another circadian output not yet investigated in the camel, may provide further information on such specific entrainment. To verify if daily LA is an endogenous rhythm and whether the desert Ta-cycle can entrain it, six dromedaries were first kept under total darkness and constant-Ta. Results showed that the LA rhythm free runs with a period of 24.8–24.9 h. After having verified that the light–dark cycle synchronizes LA, camels were subjected to a Ta-cycle with warmer temperatures during subjective days and cooler temperatures during subjective nights. Results showed that the free-running LA rhythm was entrained by the Ta-cycle with a period of exactly 24.0 h, while a 12 h Ta-cycle phase advance induced an inversion of the LA rhythm and advanced the acrophase by 9 h. Similarly, activity onset and offset were significantly advanced. All together, these results demonstrate that the Ta-cycle is a strong zeitgeber, able to entrain the camel LA rhythm, hence corroborating previous results concerning the Ta non-photic synchronization of the circadian master clock.

99mTc-HMPAO SPECT imaging reveals brain hypoperfusion during status epilepticus

Status epilepticus (SE) is a clinical emergency with high mortality. SE can trigger neuronal death or injury and alteration of neuronal networks resulting in long-term cognitive decline or epilepsy. Among the multiple factors contributing to this damage, imbalance between oxygen and glucose requirements and brain perfusion during SE has been proposed. Herein, we aimed to quantify by neuroimaging the spatiotemporal course of brain perfusion during and after lithium-pilocarpine-induced SE in rats. To this purpose, animals underwent 99mTc-HMPAO SPECT imaging at different time points during and after SE using a small animal SPECT/CT system. 99mTc-HMPAO regional uptake was normalized to the injected dose. In addition, voxel-based statistical parametric mapping was performed. SPECT imaging showed an increase of cortical perfusion before clinical seizure activity onset followed by regional hypo-perfusion starting with the first convulsive seizure and during SE. Twenty-four hours after SE, brain 99mTc-HMPAO uptake was widely decreased. Finally, chronic epileptic animals showed regionally decreased perfusion affecting hippocampus and cortical sub-regions. Despite elevated energy and oxygen requirements, brain hypo-perfusion is present during SE. Our results suggest that insufficient compensation of required blood flow might contribute to the neuronal damage and neuroinflammation, and ultimately to chronic epilepsy generated by SE.

Selective electrochemical production of hydrogen peroxide at zigzag edges of exfoliated molybdenum telluride nanoflakes

The two-electron reduction of molecular oxygen represents an effective strategy to enable the green, mild and on-demand synthesis of hydrogen peroxide. Its practical viability, however, hinges on the development of advanced electrocatalysts, preferably composed of non-precious elements, to selectively expedite this reaction, particularly in acidic medium. Our study here introduces 2H-MoTe2 for the first time as the efficient non-precious-metal-based electrocatalyst for the electrochemical production of hydrogen peroxide in acids. We show that exfoliated 2H-MoTe2 nanoflakes have high activity (onset overpotential ∼140 mV and large mass activity of 27 A g−1 at 0.4 V versus reversible hydrogen electrode), great selectivity (H2O2 percentage up to 93%) and decent stability in 0.5 M H2SO4. Theoretical simulations evidence that the high activity and selectivity of 2H-MoTe2 arise from the proper binding energies of HOO* and O* at its zigzag edges that jointly favor the two-electron reduction instead of the four-electron reduction of molecular oxygen.

CO-driven activity constrains the origin of comets

Context. An open question in the study of comets is the so-called cohesion bottleneck, that is, how dust particles detach from the nucleus. Aims. We test whether the CO pressure buildup inside the pebbles of which cometary nuclei consist can overcome this cohesion bottleneck. Methods. A recently developed pebble-diffusion model was applied here to comet C/2017K2 PANSTARRS, assuming a CO-driven activity. Results. (i) The CO-gas pressure inside the pebbles erodes the nucleus into the observed dust, which is composed of refractories, H2O ice and CO2 ice. (ii) The CO-driven activity onset occurs up to heliocentric distances of 85 au, depending on the spin orientation of the comet nucleus. (iii) The activity onset observed at ≈26 au suggests a low obliquity of the nucleus spin axis with activity in a polar summer. (iv) At 14 au, the smallest size of the ejected dust is ≈0.1 mm, consistent with observations. (v) The observed dust-loss rate of ≈200 kg s−1 implies a fallout ≥30%, a nucleus surface active area ≥10 km2, a CO-gas loss rate ≥10 kg s−1, and a dust-to-gas ratio ≤20. (vi) The CO-driven activity never stops if the average refractory-to-all-ices mass ratio in the nucleus is ≤4.5 for a nucleus all-ices-to-CO mass ratio ≈4, as observed in comets Hale–Bopp and Hyakutake. These results make comet C/2017K2 similar to the Rosetta target comet 67P/Churyumov–Gerasimenko. (vii) The erosion lifetime of cometary planetesimals is a factor 103 shorter than the timescale of catastrophic collisions. This means that the comets we observe today cannot be products of catastrophic collisions.