Serum Amyloid A Protein as a Potential Biomarker for Severity and Acute Outcome in Traumatic Brain Injury

Traumatic brain injury (TBI) causes a wide variety of neuroinflammatory events. These neuroinflammatory events depend, to a greater extent, on the severity of the damage. Our previous studies have shown that the liver produces serum amyloid A (SAA) at high levels in the initial hours after controlled cortical impact (CCI) injury in mice. Clinical studies have reported detectable SAA in the plasma of brain injury patients, but it is not clear if SAA levels depend on TBI severity. To evaluate this question, we performed a mild to severe CCI injury in wild-type mice. We collected blood samples and brains at 1, 3, and 7 days after injury for protein detection by western blotting, enzyme-linked immunosorbent assay, or immunohistochemical analysis. Our results showed that severe CCI injury compared to mild CCI injury or sham mice caused an increased neuronal death, larger lesion volume, increased microglia/macrophage density, and augmented neutrophil infiltration. Furthermore, we found that the serum levels of SAA protein ascended in the blood in correlation with high neuroinflammatory and neurodegenerative responses. Altogether, these results suggest that serum SAA may be a novel neuroinflammation-based, and severity-dependent, biomarker for acute TBI

Divergent Effects of Systemic and Intracollicular CB Receptor Activation Against Forebrain and Hindbrain-Evoked Seizures in Rats

Cannabinoid (CB) receptor agonists are of growing interest as targets for anti-seizure therapies. Here we examined the effect of systemic administration of the CB receptor agonist WIN 55,212-2 (WIN) against audiogenic seizures (AGSs) in the Genetically Epilepsy Prone Rat (GEPR)-3 strain, and against seizures evoked focally from the Area Tempestas (AT). We compared these results to the effect of focal administration of the CB1/2 receptor agonist CP 55940 into the deep layers of the superior colliculus (DLSC), a brain site expressing CB1 receptors. While systemic administration of WIN dose-dependently decreased AGS in GEPR-3s, it was without effect in the AT model. By contrast, intra-DLSC infusion of CP 55940 decreased seizures in both models. To determine if the effects of systemic WIN were dependent upon activation of CB1 receptors in the DSLC, we next microinjected the CB1 receptor antagonist SR141716, before WIN systemic treatment, and tested animals for AGS susceptibility. The pretreatment of the DLSC with SR141716 was without effect on its own and did not alter the anti-convulsant action of WIN systemic administration. Thus, while CB receptors in the DLSC are a potential site of anticonvulsant action, they are not necessary for the effects of systemically administered CB agonists

The Effect of Traumatic Brain Injury on Sleep Architecture and Circadian Rhythms in Mice—A Comparison of High-Frequency Head Impact and Controlled Cortical Injury

Traumatic brain injury (TBI) is a significant risk factor for the development of sleep and circadian rhythm impairments. In this study we compare the circadian rhythms and sleep patterns in the high-frequency head impact (HFHI) and controlled cortical impact (CCI) mouse models of TBI. These mouse models have different injury mechanisms key differences of pathology in brain regions controlling circadian rhythms and EEG wave generation. We found that both HFHI and CCI caused dysregulation in the diurnal expression of core circadian genes (Bmal1, Clock, Per1,2, Cry1,2) at 24 h post-TBI. CCI mice had reduced locomotor activity on running wheels in the first 7 d post-TBI; however, both CCI and HFHI mice were able to maintain circadian behavior cycles even in the absence of light cues. We used implantable EEG to measure sleep cycles and brain activity and found that there were no differences in the time spent awake, in NREM or REM sleep in either TBI model. However, in the sleep states, CCI mice have reduced delta power in NREM sleep and reduced theta power in REM sleep at 7 d post-TBI. Our data reveal that different types of brain trauma can result in distinct patterns of circadian and sleep disruptions and can be used to better understand the etiology of sleep disorders after TBI

Searching for Novel Drug Targets (semester?), IPRO 318: Searching for Novel Drug Targets IPRO 318 Poster F07

Over the course of the term, IPRO 318 made progress in the “[Search] for Novel Drug Targets.” This IPRO is part of an ongoing effort to try to find potential drug targets on pathogenic proteins. During past terms, IPRO 318 has compiled information on proteins that are known to be involved in diseases in a disease gene database. By comparing this to a database of hypothetical genes, possible high value proteins were found. This term IPRO 318 continued the lab work on the high value proteins found in previous semesters, found new ones and began lab work on those proteins, continued work on the databases, and started a new allergen database.Deliverables for IPRO 318: Searching for Novel Drug Targets for the Fall 2007 semeste

Searching for Novel Drug Targets (semester?), IPRO 318

Over the course of the term, IPRO 318 made progress in the “[Search] for Novel Drug Targets.” This IPRO is part of an ongoing effort to try to find potential drug targets on pathogenic proteins. During past terms, IPRO 318 has compiled information on proteins that are known to be involved in diseases in a disease gene database. By comparing this to a database of hypothetical genes, possible high value proteins were found. This term IPRO 318 continued the lab work on the high value proteins found in previous semesters, found new ones and began lab work on those proteins, continued work on the databases, and started a new allergen database.Deliverables for IPRO 318: Searching for Novel Drug Targets for the Fall 2007 semeste

Searching for Novel Drug Targets (semester?), IPRO 318: Searching for Novel Drug Targets IPRO 318 Final Report F07

Over the course of the term, IPRO 318 made progress in the “[Search] for Novel Drug Targets.” This IPRO is part of an ongoing effort to try to find potential drug targets on pathogenic proteins. During past terms, IPRO 318 has compiled information on proteins that are known to be involved in diseases in a disease gene database. By comparing this to a database of hypothetical genes, possible high value proteins were found. This term IPRO 318 continued the lab work on the high value proteins found in previous semesters, found new ones and began lab work on those proteins, continued work on the databases, and started a new allergen database.Deliverables for IPRO 318: Searching for Novel Drug Targets for the Fall 2007 semeste

Silver Nanoparticles Indicators of Thermal History (Semester Unknown) IPRO 317: SilverNanoParticlesIndicatorsOfThermalHistoryIPRO317ProjectPlanSp09

A. The primary purpose of IPRO 317 is to prove the merit of using silver nanorods as a thermal history indicator. The extended purpose of IPRO 317 is to convert the production of silver nanorods from a batch process to a continuous flow process. B. To accomplish this our team will:  Gain deeper understanding of batch process.  Research continuous flow processes with an emphasis on microreactors 6  Design and simulate a continuous flow process for production of silver nanorods with the aid of a computer simulation software.Deliverable

Silver Nanoparticles Indicators of Thermal History (Semester Unknown) IPRO 317: SilverNanoParticlesIndicatorsOfThermalHistoryIPRO317PosterSp09

A. The primary purpose of IPRO 317 is to prove the merit of using silver nanorods as a thermal history indicator. The extended purpose of IPRO 317 is to convert the production of silver nanorods from a batch process to a continuous flow process. B. To accomplish this our team will:  Gain deeper understanding of batch process.  Research continuous flow processes with an emphasis on microreactors 6  Design and simulate a continuous flow process for production of silver nanorods with the aid of a computer simulation software.Deliverable

Silver Nanoparticles Indicators of Thermal History (Semester Unknown) IPRO 317

A. The primary purpose of IPRO 317 is to prove the merit of using silver nanorods as a thermal history indicator. The extended purpose of IPRO 317 is to convert the production of silver nanorods from a batch process to a continuous flow process. B. To accomplish this our team will:  Gain deeper understanding of batch process.  Research continuous flow processes with an emphasis on microreactors 6  Design and simulate a continuous flow process for production of silver nanorods with the aid of a computer simulation software.Deliverable