Epilepsy Therapy Goes Viral.

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LOCAL SYNAPTIC NETWORK INTERACTIONS IN THE DENTATE GYRUS OF A CORTICAL CONTUSION MODEL OF POSTTRAUMATIC EPILEPSY

Posttraumatic epilepsy is a common consequence of brain trauma. However, little is known about how long-term changes in local excitatory and inhibitory synaptic networks contribute to epilepsy after closed-head brain injury. This study adapted a widely used model of experimental brain injury as a mouse model of posttraumatic epilepsy. Behavioral seizure activity and alterations in synaptic circuitry in the dentate gyrus were examined in mice after experimental cortical contusion brain injury. Spontaneous behavioral seizures were observed in 20% of mice after moderate injury and 36-40% of mice weeks after severe injury. In the dentate gyrus, most mice displayed regionally localized mossy fiber reorganization ipsilateral to the injury that was absent in control mice or sections contralateral to the injury. Extracellular field and whole-cell patch clamp recordings were performed in acute brain slice preparations of the dentate gyrus. Dentate granule cells displayed spontaneous and evoked activity that was consistent with network synchronization and the formation of recurrent excitatory network only in slices that had posttraumatic mossy fiber sprouting. The excitability of surviving hilar GABAergic interneurons, which provide important feedback inhibition to granule cells, was examined at similar time points. Cell-attached and whole-cell voltage-clamp recordings revealed increased spontaneous and glutamate photostimulation-evoked excitatory input to hilar GABA neurons ipsilateral to the injury, versus control and contralateral slices. Despite increased excitatory synaptic input to interneurons, whole-cell voltage-clamp recordings revealed a reduction in inhibitory synaptic input to granule cells. These findings suggest that there are alterations in excitatory and inhibitory circuits in mice with posttraumatic mossy fiber sprouting and seizures after cortical contusion head injury

Neural circuit mechanisms of post–traumatic epilepsy

Traumatic brain injury (TBI) greatly increases the risk for a number of mental health problems and is one of the most common causes of medically intractable epilepsy in humans. Several models of TBI have been developed to investigate the relationship between trauma, seizures, and epilepsy-related changes in neural circuit function. These studies have shown that the brain initiates immediate neuronal and glial responses following an injury, usually leading to significant cell loss in areas of the injured brain. Over time, long-term changes in the organization of neural circuits, particularly in neocortex and hippocampus, lead to an imbalance between excitatory and inhibitory neurotransmission and increased risk for spontaneous seizures. These include alterations to inhibitory interneurons and formation of new, excessive recurrent excitatory synaptic connectivity. Here, we review in vivo models of TBI as well as key cellular mechanisms of synaptic reorganization associated with post-traumatic epilepsy (PTE). The potential role of inflammation and increased blood–brain barrier permeability in the pathophysiology of PTE is also discussed. A better understanding of mechanisms that promote the generation of epileptic activity versus those that promote compensatory brain repair and functional recovery should aid development of successful new therapies for PTE

Synaptic Reorganization of Inhibitory Hilar Interneuron Circuitry After Traumatic Brain Injury in Mice

Functional plasticity of synaptic networks in the dentate gyrus has been implicated in the development of posttraumatic epilepsy and in cognitive dysfunction after traumatic brain injury, but little is known about potentially pathogenic changes in inhibitory circuits. We examined synaptic inhibition of dentate granule cells and excitability of surviving GABAergic hilar interneurons 8–13 weeks after cortical contusion brain injury in transgenic mice that express enhanced green fluorescent protein in a subpopulation of inhibitory neurons. Whole-cell voltage-clamp recordings in granule cells revealed a reduction in spontaneous and miniature IPSC frequency after head injury; no concurrent change in paired-pulse ratio was found in granule cells after paired electrical stimulation of the hilus. Despite reduced inhibitory input to granule cells, action potential and EPSC frequencies were increased in hilar GABA neurons from slices ipsilateral to the injury versus those from control or contralateral slices. Furthermore, increased excitatory synaptic activity was detected in hilar GABA neurons ipsilateral to the injury after glutamate photostimulation of either the granule cell or CA3 pyramidal cell layers. Together, these findings suggest that excitatory drive to surviving hilar GABA neurons is enhanced by convergent input from both pyramidal and granule cells, but synaptic inhibition of granule cells is not fully restored after injury. This rewiring of circuitry regulating hilar inhibitory neurons may reflect an important compensatory mechanism, but it may also contribute to network destabilization by increasing the relative impact of surviving individual interneurons in controlling granule cell excitability in the posttraumatic dentate gyrus

Quantifying non-star formation associated 8um dust emission in NGC 628

Combining Ha and IRAC images of the nearby spiral galaxy NGC 628, we find that between 30-43% of its 8um dust emission is not related to recent star formation. Contributions from dust heated by young stars are separated by identifying HII regions in the Ha map and using these areas as a mask to determine the 8um dust emission that must be due to heating by older stars. Corrections are made for sub-detection-threshold HII regions, photons escaping from HII regions and for young stars not directly associated to HII regions (i.e. 10-100 Myr old stars). A simple model confirms this amount of 8um emission can be expected given dust and PAH absorption cross-sections, a realistic star-formation history, and the observed optical extinction values. A Fourier power spectrum analysis indicates that the 8um dust emission is more diffuse than the Ha emission (and similar to observed HI), supporting our analysis that much of the 8um-emitting dust is heated by older stars. The 8um dust-to-Ha emission ratio declines with galactocentric radius both within and outside of HII regions, probably due to a radial increase in disk transparency. In the course of this work, we have also found that intrinsic diffuse Ha fractions may be lower than previously thought in galaxies, if the differential extinction between HII regions and diffuse regions is taken into account.Comment: 14 pages, 11 figures, accepted in Ap

Influence of duration of dietary vitamin E supplementation on swine growth performance and carcass quality

Supplementing medium-lean genotype pigs with supranutritional concentrations of dietary vitamin E (91 IU d-a-tocopheryl acetate/lb of feed) for as long as 70 d during the finishing phase was not effective in improving swine performance, feeding characteristics, and 24 h loin muscle quality. However, lower carcass temperatures obtained by spray chilling pork sides at O°C versus 4.4°C had a beneficial effect on 24 h carcass quality by improving marbling and lean firmness scores and reducing loin muscle moisture exudate. Overall, 24 h pork carcass quality was impacted more by chill rate than dietary vitamin E supplementation.; Swine Day, Manhattan, KS, November 19, 199

Vibrational dynamics of confined granular material

By means of two-dimensional contact dynamics simulations, we analyze the vibrational dynamics of a confined granular layer in response to harmonic forcing. We use irregular polygonal grains allowing for strong variability of solid fraction. The system involves a jammed state separating passive (loading) and active (unloading) states. We show that an approximate expression of the packing resistance force as a function of the displacement of the free retaining wall from the jamming position provides a good description of the dynamics. We study in detail the scaling of displacements and velocities with loading parameters. In particular, we find that, for a wide range of frequencies, the data collapse by scaling the displacements with the inverse square of frequency, the inverse of the force amplitude and the square of gravity. Interestingly, compaction occurs during the extension of the packing, followed by decompaction in the contraction phase. We show that the mean compaction rate increases linearly with frequency up to a characteristic frequency and then it declines in inverse proportion to frequency. The characteristic frequency is interpreted in terms of the time required for the relaxation of the packing through collective grain rearrangements between two equilibrium states