Molecular and Cellular Neuroscience Commons^™

Prolonged Cyclooxygenase-2 Induction In Neurons And Glia Following Traumatic Brain Injury In The Rat, K I Strauss, M F Barbe, R M Marshall Demarest, R Raghupathi, S Mehta, R K Narayan

Rowan-Virtua School of Osteopathic Medicine Faculty Scholarship

Cyclooxygenase-2 (COX2) is a primary inflammatory mediator that converts arachidonic acid into precursors of vasoactive prostaglandins, producing reactive oxygen species in the process. Under normal conditions COX2 is not detectable, except at low abundance in the brain. This study demonstrates a distinctive pattern of COX2 increases in the brain over time following traumatic brain injury (TBI). Quantitative lysate ribonuclease protection assays indicate acute and sustained increases in COX2 mRNA in two rat models of TBI. In the lateral fluid percussion model, COX2 mRNA is significantly elevated (>twofold, p < 0.05, Dunnett) at 1 day postinjury in the injured cortex and bilaterally in the hippocampus, compared to sham-injured controls. In the lateral cortical impact model (LCI), COX2 mRNA peaks around 6 h postinjury in the ipsilateral cerebral cortex (fivefold induction, p < 0.05, Dunnett) and in the ipsilateral and contralateral hippocampus (two- and six-fold induction, respectively, p < 0.05, Dunnett). Increases are sustained out to 3 days postinjury in the injured cortex in both models. Further analyses use the LCI model to evaluate COX2 induction. Immunoblot analyses confirm increased levels of COX2 protein in the cortex and hippocampus. Profound increases in COX2 protein are observed in the cortex at 1-3 days, that return to sham levels by 7 days postinjury (p < 0.05, Dunnett). The cellular pattern of COX2 induction following TBI has been characterized using immunohistochemistry. COX2-immunoreactivity (-ir) rises acutely (cell numbers and intensity) and remains elevated for several days following TBI. Increases in COX2-ir colocalize with neurons (MAP2-ir) and glia (GFAP-ir). Increases in COX2-ir are observed in cerebral cortex and hippocampus, ipsilateral and contralateral to injury as early as 2 h postinjury. Neurons in the ipsilateral parietal, perirhinal and piriform cortex become intensely COX2-ir from 2 h to at least 3 days postinjury. In agreement with the mRNA and immunoblot results, COX2-ir appears greatest in the contralateral hippocampus. Hippocampal COX2-ir progresses from the pyramidal cell layer of the CA1 and CA2 region at 2 h, to the CA3 pyramidal cells and dentate polymorphic and granule cell layers by 24 h postinjury. These increases are distinct from those observed following inflammatory challenge, and correspond to brain areas previously identified with the neurological and cognitive deficits associated with TBI. While COX2 induction following TBI may result in selective beneficial responses, chronic COX2 production may contribute to free radical mediated cellular damage, vascular dysfunction, and alterations in cellular metabolism. These may cause secondary injuries to the brain that promote neuropathology and worsen behavioral outcome.

The Role Of Serotonin2 Receptors In Mediating Cocaine-Induced Convulsions, Laura O'Dell

Laura Elena O'Dell

No abstract provided.

Molecular Mechanisms Mediating Genetic Sensitivity To Cocaine-Induced Convulsions., Laura O'Dell

Laura Elena O'Dell

No abstract provided.

Antidepressant Drugs Appear To Enhance Cocaine-Induced Toxicity, Laura O'Dell

Laura Elena O'Dell

No abstract provided.

Effects Of Apolipoprotein E On Olfactory Neuron Plasticity In Mice, Rafia Nisar

Masters Theses

Previous studies have shown that apoE is upregulated in injured nerves, and that it may participate in nerve regeneration by recycling lipids from the degenerating myelin sheath to axonal growth cones. However, these studies fail to differentiate apoE function in degeneration and regeneration, because of temporal juxtaposition of degeneration and regeneration in these models. In this study, we characterized the apoE expression during olfactory nerve regeneration in mice, which occurs over an extended seven week period. Olfactory nerves were lesioned in 2-3-month-old mice by intransal irrigation of Triton X-100. Following lesioning the olfactory bulbs were collected at 0, 3, 7, …

Relationship Between Protective Effects Of Estrogen, Apoe And Alzheimer's Disease, Sara M. Ludwig

Masters Theses

Alzheimer's disease (AD) is a neurodegerative disorder characterized by progressive memory loss and loss of cognitive function. The pathogenesis and progression of AD is poorly understood. Recently, several risk factors have been determined, however, how these risk factors function to induce AD onset has yet to be elucidated.

Apolipoprotein E genotype has been clearly demonstrated to be a risk factor for AD. The apoE2 and apoE3 isoforms appear to be protective against AD, whereas the apoE4 isoform has been implicated in the development of AD. The apoE4 allele works in a dosage-dependent fashion; that is, the greater the expression of …

Effects Of Apolipoprotein E On Neurite Outgrowth From Adult Mice Cortical Neurons, Yanwen Jiang

Masters Theses

Apolipoprotein (apo) E4, one of the three common isoforms of apoE, has been implicated in Alzheimer's disease (AD). The mechanism whereby apoE4 leads to the pathogenesis of AD is unknown. In the present study, I examined the effects of apoE on neurite outgrowth from adult mice cortical neurons (AMC) in culture. I found that neurite outgrowth from AMC neurons derived from apoE deficient/apoE gene knockout (apoE KO) mice is significantly shorter than that from age-, sex-, and strain-matched wild-type control mice. Furthermore, I present evidence for the differential effects of two isoforms of human apoE, apoE3 and apoE4, on neurite …

N-Methyl-D-Aspartate Receptor Subunit Nr2b Is Widely Expressed Throughout The Rat Diencephalon: An Immunohistochemical Study, Arshad Khan, B. Glenn Stanley, Lisa Bozzetti, Christina Chin, Cyndi Stivers, Margarita Curras-Collazo

Arshad M. Khan, Ph.D.

No abstract provided.