Newly born dentate granule neurons after pilocarpine-induced epilepsy have hilar basal dendrites with immature synapses.

Neurogenesis in the subgranular zone of the dentate gyrus persists throughout the lifespan of mammals, and the resulting newly born neurons are incorporated into existing hippocampal circuitry. Seizures increase the rate of neurogenesis in the adult rodent brain and result in granule cells in the dentate gyrus with basal dendrites. Using doublecortin (DCX) immunocytochemistry to label newly generated neurons the current study focuses on the electron microscopic features of DCX-labeled cell bodies and dendritic processes in the dentate gyrus of rats with pilocarpine-induced epilepsy. At the base of the granule cell layer clusters of cells that include up to six DCX-labeled cell bodies were observed. The cell bodies in these clusters lacked a one-to-one association with an astrocyte cell body and its processes, a relationship that is typical for newly born granule cells in control rats. Also, DCX-labeled basal dendrites in the hilus had immature synapses while those in control rats lacked synapses. These results indicate that increased neurogenesis after seizures alters the one-to-one relationship between astrocytes and DCX-labeled newly generated neurons at the base of the granule cell layer. The data also suggest that the synapses on DCX-labeled hilar basal dendrites contribute to the persistence of hilar basal dendrites on neurons born after pilocarpine-induced seizures

Early TBI-Induced Cytokine Alterations are Similarly Detected by Two Distinct Methods of Multiplex Assay

Annually, more than a million persons experience traumatic brain injury (TBI) in the US and a substantial proportion of this population develop debilitating neurological disorders, such as, paralysis, cognitive deficits, and epilepsy. Despite the long-standing knowledge of the risks associated with TBI, no effective biomarkers or interventions exist. Recent evidence suggests a role for inflammatory modulators in TBI-induced neurological impairments. Current technological advances allow for the simultaneous analysis of the precise spatial and temporal expression patterns of numerous proteins in single samples which ultimately can lead to the development of novel treatments. Thus, the present study examined 23 different cytokines, including chemokines, in the ipsi and contralateral cerebral cortex of rats at 24 h after a fluid percussion injury (FPI). Furthermore, the estimation of cytokines were performed in a newly developed multiplex assay instrument, MAGPIX (Luminex Corp), and compared with an established instrument, Bio-Plex (Bio-Rad), in order to validate the newly developed instrument. The results show numerous inflammatory changes in the ipsi and contralateral side after FPI that were consistently reported by both technologies

Spatiotemporal profile of dendritic outgrowth from newly born granule cells in the adult rat dentate gyrus.

Neurogenesis in the adult dentate gyrus occurs in the subgranular zone where newborn neurons (NNs) migrate a short distance into the granule cell layer and extend their rudimentary apical dendritic processes upon a radial glial scaffold. Using doublecortin (DCX) immunocytochemistry, these growing dendrites can be visualized because dendritic growth cones, including filipodia and lamellipodia, are labeled in both light and electron microscopic preparations. To study the rate of dendritic outgrowth of newborn dentate granule cells, single injections of 5-bromo-2-deoxyuridine (BrdU) with different survival times were combined with double immunolabeling for BrdU and DCX. At the earliest time points (4 and 12 h after BrdU injections), a rudimentary process can be observed to emanate from BrdU/DCX double-labeled cells. By 48 h the dendrites first appeared in the molecular layer. By 96 h after BrdU injection, these apical dendrites extended into the middle of the molecular layer where they ramified. The calculated rate of dendritic growth for NNs was about 15 microm per day for the first 3 days, and then a doubling in length occurred at 4 and 5 days that coincided with a retraction of the basal dendrite. In addition, electron microscopy of DCX-labeled apical dendrites showed that they were much thinner (1/4 to 1/3 the size) in diameter than unlabeled, mature apical dendrites and that they had developing synapses on them in the molecular layer

Synaptic connections of hilar basal dendrites of dentate granule cells in a neonatal hypoxia model of epilepsy.

Numerous animal models of epileptogenesis demonstrate neuroplastic changes in the hippocampus. These changes occur not only for the mature neurons and glia, but also for the newly generated granule cells in the dentate gyrus. One of these changes, the sprouting of mossy fiber axons, is derived predominantly from newborn granule cells in adult rats with pilocarpine-induced temporal lobe epilepsy. Newborn granule cells also mainly contribute to another neuroplastic change, hilar basal dendrites (HBDs), which are synaptically targeted by mossy fibers in the hilus. Both sprouted mossy fibers and HBDs contribute to recurrent excitatory circuitry that is hypothesized to be involved in increased seizure susceptibility and the development of spontaneous recurrent seizures (SRS) that occur following the initial pilocarpine-induced status epilepticus. Considering the putative role of these neuroplastic changes in epileptogenesis, a critical question is whether similar anatomic phenomena occur after epileptogenic insults to the immature brain, where the proportion of recently born granule cells is higher due to ongoing maturation. The current study aimed to determine if such neuroplastic changes could be observed in a standardized model of neonatal seizure-inducing hypoxia that results in development of SRS. We used immunoelectron microscopy for the immature neuronal marker doublecortin to label newborn neurons and their HBDs following neonatal hypoxia. Our goal was to determine whether synapses form on HBDs from neurons born after neonatal hypoxia. Our results show a robust synapse formation on HBDs from animals that experienced neonatal hypoxia, regardless of whether the animals experienced tonic-clonic seizures during the hypoxic event. In both cases, the axon terminals that synapse onto HBDs were identified as mossy fiber terminals, based on the appearance of dense core vesicles. No such synapses were observed on HBDs from newborn granule cells obtained from sham animals analyzed at the same time points. This aberrant circuit formation may provide an anatomic substrate for increased seizure susceptibility and the development of epilepsy

The Aviation System Analysis Capability Airport Capacity and Delay Models

The ASAC Airport Capacity Model and the ASAC Airport Delay Model support analyses of technologies addressing airport capacity. NASA's Aviation System Analysis Capability (ASAC) Airport Capacity Model estimates the capacity of an airport as a function of weather, Federal Aviation Administration (FAA) procedures, traffic characteristics, and the level of technology available. Airport capacity is presented as a Pareto frontier of arrivals per hour versus departures per hour. The ASAC Airport Delay Model allows the user to estimate the minutes of arrival delay for an airport, given its (weather dependent) capacity. Historical weather observations and demand patterns are provided by ASAC as inputs to the delay model. The ASAC economic models can translate a reduction in delay minutes into benefit dollars

Collapse to Black Holes in Brans-Dicke Theory: I. Horizon Boundary Conditions for Dynamical Spacetimes

We present a new numerical code that evolves a spherically symmetric configuration of collisionless matter in the Brans-Dicke theory of gravitation. In this theory the spacetime is dynamical even in spherical symmetry, where it can contain gravitational radiation. Our code is capable of accurately tracking collapse to a black hole in a dynamical spacetime arbitrarily far into the future, without encountering either coordinate pathologies or spacetime singularities. This is accomplished by truncating the spacetime at a spherical surface inside the apparent horizon, and subsequently solving the evolution and constraint equations only in the exterior region. We use our code to address a number of long-standing theoretical questions about collapse to black holes in Brans-Dicke theory.Comment: 46 pages including figures, uuencoded gz-compressed postscript, Submitted to Phys Rev

Effects of S100B on Serotonergic Plasticity and Neuroinflammation in the Hippocampus in Down Syndrome and Alzheimer's Disease: Studies in an S100B Overexpressing Mouse Model

S100B promotes development and maturation in the mammalian brain. However, prolonged or extensive exposure can lead to neurodegeneration. Two important functions of S100B in this regard, are its role in the development and plasticity of the serotonergic neurotransmitter system, and its role in the cascade of glial changes associated with neuroinflammation. Both of these processes are therefore accelerated towards degeneration in disease processes wherein S100B is increased, notably, Alzheimer's disease (AD) and Down syndrome (DS). In order to study the role of S100B in this context, we have examined S100B overexpressing transgenic mice. Similar to AD and DS, the transgenic animals show a profound change in serotonin innervation. By 28 weeks of age, there is a significant loss of terminals in the hippocampus. Similarly, the transgenic animals show neuroinflammatory changes analogous with AD and DS. These include decreased numbers of mature, stable astroglial cells, increased numbers of activated microglial cells and increased microglial expression of the cell surface receptor RAGE. Eventually, the S100B transgenic animals show neurodegeneration and the appearance of hyperphosphorylated tau structures, as seen in late stage DS and AD. The role of S100B in these conditions is discussed

Scaling of the conductance distribution near the Anderson transition

The single parameter scaling hypothesis is the foundation of our understanding of the Anderson transition. However, the conductance of a disordered system is a fluctuating quantity which does not obey a one parameter scaling law. It is essential to investigate the scaling of the full conductance distribution to establish the scaling hypothesis. We present a clear cut numerical demonstration that the conductance distribution indeed obeys one parameter scaling near the Anderson transition

Tendinosis develops from age- and oxygen tension-dependent modulation of Rac1 activity.

Age-related tendon degeneration (tendinosis) is characterized by a phenotypic change in which tenocytes display characteristics of fibrochondrocytes and mineralized fibrochondrocytes. As tendon degeneration has been noted in vivo in areas of decreased tendon vascularity, we hypothesized that hypoxia is responsible for the development of the tendinosis phenotype, and that these effects are more pronounced in aged tenocytes. Hypoxic (1% O2 ) culture of aged, tendinotic, and young human tenocytes resulted in a mineralized fibrochondrocyte phenotype in aged tenocytes, and a fibrochondrocyte phenotype in young and tendinotic tenocytes. Investigation of the molecular mechanism responsible for this phenotype change revealed that the fibrochondrocyte phenotype in aged tenocytes occurs with decreased Rac1 activity in response to hypoxia. In young hypoxic tenocytes, however, the fibrochondrocyte phenotype occurs with concomitant decreased Rac1 activity coupled with increased RhoA activity. Using pharmacologic and adenoviral manipulation, we confirmed that these hypoxic effects on the tenocyte phenotype are linked directly to the activity of RhoA/Rac1 GTPase in in vitro human cell culture and tendon explants. These results demonstrate that hypoxia drives tenocyte phenotypic changes, and provide a molecular insight into the development of human tendinosis that occurs with aging