Gene expression patterns following unilateral traumatic brain injury reveals a local pro-inflammatory and remote anti-inflammatory response.

BackgroundTraumatic brain injury (TBI) results in irreversible damage at the site of impact and initiates cellular and molecular processes that lead to secondary neural injury in the surrounding tissue. We used microarray analysis to determine which genes, pathways and networks were significantly altered using a rat model of TBI. Adult rats received a unilateral controlled cortical impact (CCI) and were sacrificed 24 h post-injury. The ipsilateral hemi-brain tissue at the site of the injury, the corresponding contralateral hemi-brain tissue, and naïve (control) brain tissue were used for microarray analysis. Ingenuity Pathway Analysis (IPA) software was used to identify molecular pathways and networks that were associated with the altered gene expression in brain tissues following TBI.ResultsInspection of the top fifteen biological functions in IPA associated with TBI in the ipsilateral tissues revealed that all had an inflammatory component. IPA analysis also indicated that inflammatory genes were altered on the contralateral side, but many of the genes were inversely expressed compared to the ipsilateral side. The contralateral gene expression pattern suggests a remote anti-inflammatory molecular response. We created a network of the inversely expressed common (i.e., same gene changed on both sides of the brain) inflammatory response (IR) genes and those IR genes included in pathways and networks identified by IPA that changed on only one side. We ranked the genes by the number of direct connections each had in the network, creating a gene interaction hierarchy (GIH). Two well characterized signaling pathways, toll-like receptor/NF-kappaB signaling and JAK/STAT signaling, were prominent in our GIH.ConclusionsBioinformatic analysis of microarray data following TBI identified key molecular pathways and networks associated with neural injury following TBI. The GIH created here provides a starting point for investigating therapeutic targets in a ranked order that is somewhat different than what has been presented previously. In addition to being a vehicle for identifying potential targets for post-TBI therapeutic strategies, our findings can also provide a context for evaluating the potential of therapeutic agents currently in development

Introduction to Homogenous Catalysis with Ruthenium-Catalyzed Oxidation of Alcohols: An Experiment for Undergraduate Advanced Inorganic Chemistry Students

A three-week laboratory experiment, which introduces students in an advanced inorganic chemistry course to air-sensitive chemistry and catalysis, is described. During the first week, the students synthesize RuCl2(PPh3)3. During the second and third weeks, the students characterize the formed coordination compound and use it as a precatalyst for the oxidation of 1-phenylethanol to acetophenone. The synthesized RuCl2(PPh3)3 is characterized using 1H and 31P NMR spectroscopy, IR spectroscopy, and magnetic susceptibility measurements. The students run catalytic and control reactions and determine the percent yield of the product using 1H NMR. The synthesis and catalytic conditions are modified from previously published research articles. The RuCl2(PPh3)3 complex is air sensitive and is prepared under a nitrogen gas atmosphere and worked up in an inert atmosphere glovebox. The catalytic and control reactions are set up in the inert atmosphere glovebox and carried out at reflux outside of the glovebox under a nitrogen gas atmosphere. In this laboratory, the students learn how to set up and run a reaction under a nitrogen atmosphere, how to work in a glovebox, and how to set up and characterize catalytic and control reactions

New Mechanics of Traumatic Brain Injury

The prediction and prevention of traumatic brain injury is a very important aspect of preventive medical science. This paper proposes a new coupled loading-rate hypothesis for the traumatic brain injury (TBI), which states that the main cause of the TBI is an external Euclidean jolt, or SE(3)-jolt, an impulsive loading that strikes the head in several coupled degrees-of-freedom simultaneously. To show this, based on the previously defined covariant force law, we formulate the coupled Newton-Euler dynamics of brain's micro-motions within the cerebrospinal fluid and derive from it the coupled SE(3)-jolt dynamics. The SE(3)-jolt is a cause of the TBI in two forms of brain's rapid discontinuous deformations: translational dislocations and rotational disclinations. Brain's dislocations and disclinations, caused by the SE(3)-jolt, are described using the Cosserat multipolar viscoelastic continuum brain model. Keywords: Traumatic brain injuries, coupled loading-rate hypothesis, Euclidean jolt, coupled Newton-Euler dynamics, brain's dislocations and disclinationsComment: 18 pages, 1 figure, Late

Shear Forces during Blast, Not Abrupt Changes in Pressure Alone, Generate Calcium Activity in Human Brain Cells

Blast-Induced Traumatic Brain Injury (bTBI) describes a spectrum of injuries caused by an explosive force that results in changes in brain function. The mechanism responsible for primary bTBI following a blast shockwave remains unknown. We have developed a pneumatic device that delivers shockwaves, similar to those known to induce bTBI, within a chamber optimal for fluorescence microscopy. Abrupt changes in pressure can be created with and without the presence of shear forces at the surface of cells. In primary cultures of human central nervous system cells, the cellular calcium response to shockwaves alone was negligible. Even when the applied pressure reached 15 atm, there was no damage or excitation, unless concomitant shear forces, peaking between 0.3 to 0.7 Pa, were present at the cell surface. The probability of cellular injury in response to a shockwave was low and cell survival was unaffected 20 hours after shockwave exposure

Adaptation of a Commercial Counter X-Ray Diffractometer for Investigations to 3000 C

A General Electric XRD-5 diffractometer equipped with a scintillation counter, a pulse height discriminator, and a modified version of the Model X-86G high-temperature diffractometer attachment, was modified for x-ray diffraction analysis at temperatures up to 3000 deg C. These modifications include frame assemblies, viewing port, filament materials, and thermocouples. (D.L.C.