Cerium Oxide Nanoparticles Improve Lifespan of Stored Blood.

Introduction: Blood is a precious commodity, with storage limited to 42 days under refrigeration. Degradative changes in red blood cells (RBCs) begin as early as 11-21 days after collection, and compromise their function. Materials that extend the life of RBCs will improve blood utilization in the field, as well as in hospital settings.

Genomic divergence and adaptive convergence in from Evolution Canyon, Israel.

Biodiversity refugia formed by unique features of the Mediterranean arid landscape, such as the dramatic ecological contrast of "Evolution Canyon," provide a natural laboratory in which local adaptations to divergent microclimate conditions can be investigated. Significant insights have been provided by studies of diversifying along the thermal gradient in Evolution Canyon, but a comparative framework to survey adaptive convergence across sister species at the site has been lacking. To fill this void, we present an analysis of genomic polymorphism and evolutionary divergence of , a close relative of with which it co-occurs on both slopes of the canyon.

Cerium oxide nanoparticles in neuroprotection and considerations for efficacy and safety.

Cerium oxide nanoparticles have widespread use in the materials industry, and have recently come into consideration for biomedical use due to their potent regenerative antioxidant properties. Given that the brain is one of the most highly oxidative organs in the body, it is subject to some of the greatest levels of oxidative stress, particularly in neurodegenerative disease. Therefore, cerium oxide nanoparticles are currently being investigated for efficacy in several neurodegenerative disorders and have shown promising levels of neuroprotection.

Cerium Oxide Nanoparticles Improve Outcome after and Mild Traumatic Brain Injury.

Mild traumatic brain injury results in aberrant free radical generation, which is associated with oxidative stress, secondary injury signaling cascades, mitochondrial dysfunction, and poor functional outcome. Pharmacological targeting of free radicals with antioxidants has been examined as an approach to treatment, but has met with limited success in clinical trials. Conventional antioxidants that are currently available scavenge a single free radical before they are destroyed in the process.

A novel bridge wire model of blast traumatic brain injury - biomed 2013.

Research into the mechanics of blast-induced traumatic brain injury requires a device capable of reproducing pressures of the same magnitude and time scale as a blast wave. A blast simulator based on the exploding bridge wire mechanism was created with these capabilities. Peak blast pressures in the range of 5 – 29 psi were generated with a positive phase duration less than 20 µs.

A new model for mild blast injury utilizing Drosophila melanogaster - biomed 2013.

Current models for blast injury involve the use of mammalian species, which are costly and require extensive monitoring and housing, making it difficult to generate large numbers of injuries. The fruit fly, Drosophila melanogaster, has been utilized for many models of human disease including neurodegenerative disorders such as Parkinson’s and Alzheimer’s diseases. In this study, a model of blast injury was designed based on Drosophila, to provide a mechanism to investigate blast injury in large numbers and assess biochemical mechanisms of brain injury.

Malathion/oxon and lead acetate increase gene expression and protein levels of transient receptor potential canonical channel subunits TRPC1 and TRPC4 in rat endothelial cells of the blood-brain barrier.

This study examined the effects of malathion and lead on transient receptor potential canonical channel TRPC1/TRPC4 channels in rat brain endothelial cells as a mechanism to explain previously noted blood-brain barrier (BBB) permeability induced by these compounds. Lead, malathion, malaoxon and combinations of these were assessed for protein levels and gene expression of TRPC1/C4 at 2, 4, 8, 16, and 24 hours after exposure. Changes in intracellular free calcium dynamics were also assessed.

Dopamine stimulates propagation of Toxoplasma gondii tachyzoites in human fibroblast and primary neonatal rat astrocyte cell cultures.

Toxoplasma gondii is an obligate intracellular parasite often found in the brain of humans. Research has shown a correlation between prevalence of antibody titers to T. gondii and psychological illness in humans.

Antioxidant nanoparticles for control of infectious disease.

The new ground being broken by the field of nanotechnology provides us with numerous prospects for treatment and prevention of infectious diseases. Recent reports have demonstrated that several types of nanoparticles act as potent free radical scavengers and antioxidants. Specific nanoconstructs are also reported to have anti-inflammatory activities.

Cadmium-containing nanoparticles: perspectives on pharmacology and toxicology of quantum dots.

The field of nanotechnology is rapidly expanding with the development of novel nanopharmaceuticals that have potential for revolutionizing medical treatment. The rapid pace of expansion in this field has exceeded the pace of pharmacological and toxicological research on the effects of nanoparticles in the biological environment. The development of cadmium-containing nanoparticles, known as quantum dots, show great promise for treatment and diagnosis of cancer and targeted drug delivery, due to their size-tunable fluorescence and ease of functionalization for tissue targeting.

Validation of an improved injury device for in vitro study of neural cell deformation - biomed 2009.

Traumatic Brain Injury is hypothesized to occur as a function of the strain and strain rate experienced by neural tissues during a traumatic event. In vitro studies of TBI at the cellular level have used a variety of methods to subject neural cell cultures to potentially injurious strains and strain rates. The Advanced Cell Deformation System (ACDS) has been developed which has the ability to independently control strain and strain rate and can strain cell cultures grown on a stretchable membrane from 0.

Development of an improved injury device for neural cell cultures.

Traumatic Brain Injury is hypothesized to occur as a function of the strain and strain rate experienced by neural tissues during a traumatic event. In vitro studies of TBI at the cellular level have used a variety of methods to subject neural cell cultures to potentially injurious strains and strain rates. A device used in previous investigations of neural cell injury was limited in its ability to control strain and strain rate independently or simulate quick repetitive loading.

Mechanical properties of polytetraflouroethylene elastomer membrane for dynamic cell culture testing.

A wide body of existing research on cellular injury has been conducted using cell cultures grown on flexible elastomer membranes deformed by a transient pressure pulse. However, there has been little published information on the material properties of these elastic membranes. In order to facilitate the development of a finite element model of cellular injury, the material properties of the underlying membrane must first be known.

Treatment of neurodegenerative disorders with radical nanomedicine.

In engineering and materials science, nanotechnology has provided many advances that effectively reduce oxidative damage generated by free radical production. Despite such advances, there has been little application to biomedical problems. Increased oxidative stress and free radical production are associated with neurodegenerative conditions, including aging, trauma, Alzheimer's and Parkinson's diseases, and many others.

Radical nanomedicine.

Nanotechnology has made significant advances in the reduction of free radical damage in the field of materials science. Cross-disciplinary interactions and the application of this technology to biological systems has led to the elucidation of novel nanoparticle antioxidants, which are the subject of this review. Recent reports suggest that cerium oxide and other nanoparticles are potent, and probably regenerative, free radical scavengers in vitro and in vivo.

Numerical simulation of a cellular-level experiment to induce traumatic injury to neurons.

Previous research has developed a pneumatically driven device for delivering a controlled mechanical insult to cultured neurons. The neuronal cell culture was injured by applying a transient air pulse to a culture well fitted with a highly elastic Silastic culture well bottom. In response to the pressure pulse, he Silastic culture well bottom deformed, stretched the attached cell culture, and resulted in observable cell injuries and death.

Nanoparticles and cell longevity.

The field of engineering has made substantial strides in nanotechnology, in the realm of materials science and construction of nanoscale devices. Nanomedicine encompasses application of cutting edge engineered nanostructures to biological systems and development of novel strategies for disease intervention. In the current review, we discuss the pharmacological application of nanoparticles as free radical scavengers and the capacity of nanoparticles to promote cell and organismal longevity.

Antagonism of group I metabotropic glutamate receptors and PLC attenuates increases in inositol trisphosphate and reduces reactive gliosis in strain-injured astrocytes.

We have previously found that in vitro traumatic injury uncouples IP3-mediated intracellular free calcium ([Ca2+]i) signaling in astrocytes (Rzigalinski et al., 1998; Floyd et al., 2001).

NMDA receptor activation contributes to a portion of the decreased mitochondrial membrane potential and elevated intracellular free calcium in strain-injured neurons.

In our previous studies, we have shown that in vitro biaxial strain (stretch) injury of neurons in neuronal plus glial cultures increases intracellular free calcium ([Ca(2+)](i)) and decreases mitochondrial membrane potential (deltapsi(m)). The goal of this study was to determine whether strain injury, without the addition of exogenous agents, causes glutamate release, and whether NMDA receptor antagonists affect the post-strain injury rise in [Ca(2+)](i) and decrease in deltapsi(m). [Ca(2+)](i) and deltapsi(m) were measured using the fluorescent indicators fura-2 AM and rhodamine-1,2,3 (rh123).

Calcium responses to caffeine and muscarinic receptor agonists are altered in traumatically injured neurons.

A fundamental mechanism that is believed to contribute to neuronal injury and death following traumatic brain injury (TBI) is a disruption in cellular calcium homeostasis. Of primary importance to these homeostatic mechanisms are intracellular calcium stores located on the endoplasmic reticulum. These intracellular stores play an important role in maintaining normal levels of calcium and calcium-mediated signaling through these stores is critical to several physiological processes in neurons.

Traumatic injury of cultured astrocytes alters inositol (1,4,5)-trisphosphate-mediated signaling.

Our previous studies using an in vitro model of traumatic injury have shown that stretch injury of astrocytes causes a rapid elevation in intracellular free calcium ([Ca2+]i), which returns to near normal by 15 min postinjury. We have also shown that after injury astrocyte intracellular calcium stores are no longer able to release Ca2+ in response to signal transduction events mediated by the second messenger inositol (1,4,5)-trisphosphate (IP3, Rzigalinski et al., 1998).

Traumatic injury of cortical neurons causes changes in intracellular calcium stores and capacitative calcium influx.

Using an in vitro traumatic injury model, we examined the effects of mechanical (stretch) injury on intracellular Ca2+ store-mediated signaling in cultured cortical neurons using fura-2. We previously found that elevation of [Ca2+](i) by the endoplasmic reticulum Ca2+-ATPase inhibitor, thapsigargin, was abolished 15 min post-injury. In the current studies, pre-injury inhibition of phospholipase C with neomycin sulfate maintained Ca2+-replete stores 15 min post-injury, suggesting that the initial injury-induced store depletion may be due to increased inositol trisphosphate production.

Astrocytes generate isoprostanes in response to trauma or oxygen radicals.

Previous studies have shown that oxygen radical scavengers prevent the reduced cerebral blood flow that occurs following experimental traumatic brain injury. The exact chemical species responsible for the posttraumatic reduction in flow is unknown. We tested whether isoprostanes, which are formed by non-cyclooxygenase-dependent free radical attack of arachidonic acid and are vasoconstrictors of the cerebral circulation, are increased in astrocytes following stretch-induced trauma or injury with a free radical generating system.

Stretch-induced injury alters mitochondrial membrane potential and cellular ATP in cultured astrocytes and neurons.

Energy deficit after traumatic brain injury (TBI) may alter ionic homeostasis, neurotransmission, biosynthesis, and cellular transport. Using an in vitro model for TBI, we tested the hypothesis that stretch-induced injury alters mitochondrial membrane potential (delta(psi)m) and ATP in astrocytes and neurons. Astrocytes, pure neuronal cultures, and mixed neuronal plus glial cultures grown on Silastic membranes were subjected to mild, moderate, and severe stretch.

Alterations in calcium-mediated signal transduction after traumatic injury of cortical neurons.

Calcium influx and elevation of intracellular free calcium ([Ca2+]i), with subsequent activation of degradative enzymes, is hypothesized to cause cell injury and death after traumatic brain injury. We examined the effects of mild-to-severe stretch-induced traumatic injury on [Ca2+]i dynamics in cortical neurons cultured on silastic membranes. [Ca2+]i was rapidly elevated after injury, however, the increase was transient with neuronal [Ca2+]i returning to basal levels by 3 h after injury, except in the most severely injured cells.