Optimized Model of Cerebral Ischemia In situ for the Long-Lasting Assessment of Hippocampal Cell Death

Among all the brain, the hippocampus is the most susceptible region to ischemic lesion, with the highest vulnerability of CA1 pyramidal neurons to ischemic damage. This damage may cause either prompt neuronal death (within hours) or with a delayed appearance (over days), providing a window for applying potential therapies to reduce or prevent ischemic impairments. However, the time course when ischemic damage turns to neuronal death strictly depends on experimental modeling of cerebral ischemia and, up to now, studies were predominantly focused on a short time-window—from hours to up to a few days post-lesion. Using different schemes of oxygen-glucose deprivation (OGD), the conditions taking place upon cerebral ischemia, we optimized a model of mimicking ischemic conditions in organotypical hippocampal slices for the long-lasting assessment of CA1 neuronal death (at least 3 weeks). By combining morphology and electrophysiology, we show that prolonged (30-min duration) OGD results in a massive neuronal death and overwhelmed astrogliosis within a week post-OGD whereas OGD of a shorter duration (10-min) triggered programmed CA1 neuronal death with a significant delay—within 2 weeks—accompanied with drastically impaired CA1 neuron functions. Our results provide a rationale toward optimized modeling of cerebral ischemia for reliable examination of potential treatments for brain neuroprotection, neuro-regeneration, or testing neuroprotective compounds in situ

Charge carrier injection into insulating media: single-particle versus mean-field approach

Self-consistent, mean-field description of charge injection into a dielectric medium is modified to account for discreteness of charge carriers. The improved scheme includes both the Schottky barrier lowering due to the individual image charge and the barrier change due to the field penetration into the injecting electrode that ensures validity of the model at both high and low injection rates including the barrier dominated and the space-charge dominated regimes. Comparison of the theory with experiment on an unipolar ITO/PPV/Au-device is presented.Comment: 32 pages, 9 figures; revised version accepted to PR

Opposite, bidirectional shifts in excitation and inhibition in specific types of dorsal horn interneurons are associated with spasticity and pain post-SCI

Spasticity, a common complication after spinal cord injury (SCI), is frequently accompanied by chronic pain. The physiological origin of this pain (critical to its treatment) remains unknown, although spastic motor dysfunction has been related to the hyperexcitability of motoneurons and to changes in spinal sensory processing. Here we show that the pain mechanism involves changes in sensory circuits of the dorsal horn (DH) where nociceptive inputs integrate for pain processing. Spasticity is associated with the DH hyperexcitability resulting from an increase in excitation and disinhibition occurring in two respective types of sensory interneurons. In the tonic-firing inhibitory lamina II interneurons, glutamatergic drive was reduced while glycinergic inhibition was potentiated. In contrast, excitatory drive was boosted to the adapting-firing excitatory lamina II interneurons while GABAergic and glycinergic inhibition were reduced. Thus, increased activity of excitatory DH interneurons coupled with the reduced excitability of inhibitory DH interneurons post-SCI could provide a neurophysiological mechanism of central sensitization and chronic pain associated with spasticity

Functional Characterization of Lamina X Neurons in ex-Vivo Spinal Cord Preparation

Functional properties of lamina X neurons in the spinal cord remain unknown despite the established role of this area for somatosensory integration, visceral nociception, autonomic regulation and motoneuron output modulation. Investigations of neuronal functioning in the lamina X have been hampered by technical challenges. Here we introduce an ex-vivo spinal cord preparation with both dorsal and ventral roots still attached for functional studies of the lamina X neurons and their connectivity using an oblique LED illumination for resolved visualization of lamina X neurons in a thick tissue. With the elaborated approach, we demonstrate electrophysiological characteristics of lamina X neurons by their membrane properties, firing pattern discharge and fiber innervation (either afferent or efferent). The tissue preparation has been also probed using Ca2+ imaging with fluorescent Ca2+ dyes (membrane-impermeable or -permeable) to demonstrate the depolarization-induced changes in intracellular calcium concentration in lamina X neurons. Finally, we performed visualization of subpopulations of lamina X neurons stained by retrograde labeling with aminostilbamidine dye to identify sympathetic preganglionic and projection neurons in the lamina X. Thus, the elaborated approach provides a reliable tool for investigation of functional properties and connectivity in specific neuronal subpopulations, boosting research of lamina X of the spinal cord

Foaming agent effect on the phosphate flotation

The foaming agent effect of different chemical nature (pine oil, T-66 reagent, alcohols, kaprol) on the phosphate flotation by carboxyl collectors was investigated. It was established that the main flotation concentrate yield, the flotation rate and extraction of useful components (P2O5) in the foam product increases during the phosphate flotation by tall oil in the presence of pine oil or hexyl alcohol with increasing its consumption

Spinal AMPA receptors: Amenable players in central sensitization for chronic pain therapy?

The activity-dependent trafficking of AMPA receptors (AMPAR) mediates synaptic strength and plasticity, while the perturbed trafficking of the receptors of different subunit compositions has been linked to memory impairment and to causing neuropathology. In the spinal cord, nociceptive-induced changes in AMPAR trafficking determine the central sensitization of the dorsal horn (DH): changes in AMPAR subunit composition compromise the balance between synaptic excitation and inhibition, rendering interneurons hyperexcitable to afferent inputs, and promoting Ca2+ influx into the DH neurons, thereby amplifying neuronal hyperexcitability. The DH circuits become over-excitable and carry out aberrant sensory processing; this causes an increase in pain sensation in central sensory pathways, giving rise to chronic pain syndrome. Current knowledge of the contribution of spinal AMPAR to the cellular mechanisms relating to chronic pain provides opportunities for developing target-based therapies for chronic pain intervention

Perpendicular Ion Heating by Low-Frequency Alfven-Wave Turbulence in the Solar Wind

We consider ion heating by turbulent Alfven waves (AWs) and kinetic Alfven waves (KAWs) with perpendicular wavelengths comparable to the ion gyroradius and frequencies smaller than the ion cyclotron frequency. When the turbulence amplitude exceeds a certain threshold, an ion's orbit becomes chaotic. The ion then interacts stochastically with the time-varying electrostatic potential, and the ion's energy undergoes a random walk. Using phenomenological arguments, we derive an analytic expression for the rates at which different ion species are heated, which we test by simulating test particles interacting with a spectrum of randomly phased AWs and KAWs. We find that the stochastic heating rate depends sensitively on the quantity epsilon = dv/vperp, where vperp is the component of the ion velocity perpendicular to the background magnetic field B0, and dv (dB) is the rms amplitude of the velocity (magnetic-field) fluctuations at the gyroradius scale. In the case of thermal protons, when epsilon << eps1, where eps1 is a constant, a proton's magnetic moment is nearly conserved and stochastic heating is extremely weak. However, when epsilon > eps1, the proton heating rate exceeds the cascade power that would be present in strong balanced KAW turbulence with the same value of dv, and magnetic-moment conservation is violated. For the random-phase waves in our test-particle simulations, eps1 is approximately 0.2. For protons in low-beta plasmas, epsilon is approximately dB/B0 divided by the square root of beta, and epsilon can exceed eps1 even when dB/B0 << eps1. At comparable temperatures, alpha particles and minor ions have larger values of epsilon than protons and are heated more efficiently as a result. We discuss the implications of our results for ion heating in coronal holes and the solar wind.Comment: 14 pages, 5 figures, submitted to Ap