An exploration into common mechanisms of oxidative damage in models of demyelinating disease and neurotrauma

This thesis explored common mechanisms of oxidative damage in multiple sclerosis and neurotrauma and encompasses work that has been published in four journal articles. Initially, the effectiveness of a combinatorial ion channel inhibitor treatment was established in models of both disorders. The cuprizone model of demyelinating disease was also optimised, followed by explorations into the relationship between oxidative DNA damage, cell proliferation and blood vessel dysfunction in models of neurotrauma and multiple sclerosis

2011 Vegetation Map for Mammoth Cave National Park

An accuracy assessment on a 2009 Vegetation Map of Mammoth Cave National Park produced by University of Georgia indicated inadequate reliability. As well, there were significant polygon boundary errors and unclassified polygons left blank on the map. With pressing need for a vegetation map to support the park’s Fire Management Plan (FMP), a derivative of the 2008 Landfire map was produced. Specifically, 24 categories were regrouped into 4 vegetation categories useful for the FMP. Barrens and Prairie Plantation categories were added as superimposed polygons, and the same approach was taken for both fire and storm-linked forest canopy gaps. Accuracy assessment data points were sampled on a random basis until the cumulative percent correct stabilized, indicating that the sample size was adequate. The final cumulative average for this map was 66% accurate, which will require enhanced field checking of prescribed fire plots. Funding will be sought for yet a new map

Oligodendroglia are particularly vulnerable to oxidative damage after neurotrauma in vivo

Loss of function following injury to the central nervous system is worsened by secondary degeneration of neurons and glia surrounding the injury and initiated by oxidative damage. However, it is not yet known which cellular populations and structures are most vulnerable to oxidative damage in vivo Using Nanoscale secondary ion mass spectrometry (NanoSIMS), oxidative damage was semi-quantified within cellular subpopulations and structures of optic nerve vulnerable to secondary degeneration, following a partial transection of the optic nerve in adult female PVG rats. Simultaneous assessment of cellular subpopulations and structures revealed oligodendroglia as the most vulnerable to DNA oxidation following injury. 5-ethynyl-2'-deoxyuridine (EdU) was used to label cells that proliferated in the first 3 days after injury. Injury led to increases in DNA, protein and lipid damage in OPCs and mature oligodendrocytes at 3 days, regardless of proliferative state, associated with a decline in the numbers of OPCs at 7 days. O4+ pre-oligodendrocytes also exhibited increased lipid peroxidation. Interestingly, EdU+ mature oligodendrocytes derived after injury demonstrated increased early susceptibility to DNA damage and lipid peroxidation. However, EdU- mature oligodendrocytes with high 8OHdG immunoreactivity were more likely to be caspase3+. By day 28, newly derived mature oligodendrocytes had significantly reduced MYRF mRNA indicating that the myelination potential of these cells may be reduced. The proportion of caspase3+ oligodendrocytes remained higher in EdU- cells. Innovative use of NanoSIMS together with traditional immunohistochemistry and in situ hybridisation have enabled the first demonstration of subpopulation specific oligodendroglial vulnerability to oxidative damage, due to secondary degeneration in vivo. SIGNIFICANCE STATEMENT. Injury to the central nervous system is characterised by oxidative damage in areas adjacent to the injury. However, the cellular subpopulations and structures most vulnerable to this damage remain to be elucidated. Here we use powerful NanoSIMS techniques to show increased oxidative damage in oligodendroglia and axons and to demonstrate that cells early in the oligodendroglial lineage are the most vulnerable to DNA oxidation. Further immunohistochemical and in situ hybridisation investigation reveals that mature oligodendrocytes derived after injury are more vulnerable to oxidative damage than their counterparts existing at the time of injury and have reduced MYRF mRNA, yet pre-existing oligodendrocytes are more likely to die

Geology of Mammoth Cave National Park, Kentucky

Mammoth Cave National Park in south-central Kentucky was authorized as a national park in 1926 and was fully established in 1941 to protect the cave system, scenic landscape, and diverse flora and fauna. The park contains 52,830 acres and most of the longest recorded cave system in the world, with more than 390 miles of mapped passages as of 2013. Even though Mammoth Cave is famous, people are often unaware of the park\u27s intricate connection to the outside region. This poster shows the geology of Mammoth Cave and the interconnected issues that are important to the park and its visitors. This cooperative project between the Kentucky Geological Survey and the National Park Service is intended for park visitors, educators, park staff, and anyone who enjoys Mammoth Cave National Park. Digital geologic mapping and recent advances in geographic information system (GIS) technologies help the National Park Service meet federal mandates and distribute data sets, maps, and other products that are valuable to all who enjoy national parks. For more information, please visit the Mammoth Cave National Park Web site at www.nps.gov/maca. You can also find information at the Mammoth Cave International Center for Science and Learning, a research and education center for the park. If you\u27re interested in obtaining digital geologic and other GIS data, visit the National Park Service Datastore at www.science.nature.nps.gov/nrdata. The geologic map data in this publication were developed from Davidson (2006), Mullins (2006a, b), Thompson (2006a, b), and Toth (2006a-d)

Secondary Degeneration of Oligodendrocyte Precursor Cells Occurs as Early as 24 h after Optic Nerve Injury in Rats

Optic nerve injury causes secondary degeneration, a sequela that spreads damage from the primary injury to adjacent tissue, through mechanisms such as oxidative stress, apoptosis, and blood-brain barrier (BBB) dysfunction. Oligodendrocyte precursor cells (OPCs), a key component of the BBB and oligodendrogenesis, are vulnerable to oxidative deoxyribonucleic acid (DNA) damage by 3 days post-injury. However, it is unclear whether oxidative damage in OPCs occurs earlier at 1 day post-injury, or whether a critical ‘window-of-opportunity’ exists for therapeutic intervention. Here, a partial optic nerve transection rat model of secondary degeneration was used with immunohistochemistry to assess BBB dysfunction, oxidative stress, and proliferation in OPCs vulnerable to secondary degeneration. At 1 day post-injury, BBB breach and oxidative DNA damage were observed, alongside increased density of DNA-damaged proliferating cells. DNA-damaged cells underwent apoptosis (cleaved caspase3+), and apoptosis was associated with BBB breach. OPCs experienced DNA damage and apoptosis and were the major proliferating cell type with DNA damage. However, the majority of caspase3+ cells were not OPCs. These results provide novel insights into acute secondary degeneration mechanisms in the optic nerve, highlighting the need to consider early oxidative damage to OPCs in therapeutic efforts to limit degeneration following optic nerve injury

Secondary Degeneration of Oligodendrocyte Precursor Cells Occurs as Early as 24 h after Optic Nerve Injury in Rats

Optic nerve injury causes secondary degeneration, a sequela that spreads damage from the primary injury to adjacent tissue, through mechanisms such as oxidative stress, apoptosis, and blood-brain barrier (BBB) dysfunction. Oligodendrocyte precursor cells (OPCs), a key component of the BBB and oligodendrogenesis, are vulnerable to oxidative deoxyribonucleic acid (DNA) damage by 3 days post-injury. However, it is unclear whether oxidative damage in OPCs occurs earlier at 1 day post-injury, or whether a critical ‘window-of-opportunity’ exists for therapeutic intervention. Here, a partial optic nerve transection rat model of secondary degeneration was used with immunohistochemistry to assess BBB dysfunction, oxidative stress, and proliferation in OPCs vulnerable to secondary degeneration. At 1 day post-injury, BBB breach and oxidative DNA damage were observed, alongside increased density of DNA-damaged proliferating cells. DNA-damaged cells underwent apoptosis (cleaved caspase3+), and apoptosis was associated with BBB breach. OPCs experienced DNA damage and apoptosis and were the major proliferating cell type with DNA damage. However, the majority of caspase3+ cells were not OPCs. These results provide novel insights into acute secondary degeneration mechanisms in the optic nerve, highlighting the need to consider early oxidative damage to OPCs in therapeutic efforts to limit degeneration following optic nerve injury