Subcortical white matter stroke is a common stroke subtype but has had limited pre-clinical modeling. Recapitulating this disease process in mice has been impeded by the relative inaccessibility of the sub-cortical white matter arterial supply to induce white matter ischemia in isolation. In this report, we detail a subcortical white matter stroke model developed in the mouse and its characterization with a comprehensive set of MRI, immunohistochemical, neuronal tract tracing and electron microscopic studies. Focal injection of the vasoconstrictor endothelin-1 into the subcortical white matter produces an infarct core that develops a maximal MRI signal by day 2, which is comparable in relative size and location to human subcortical stroke. Immunohistochemical studies indicate that oligodendrocyte apoptosis is maximal at day 1 and apoptotic cells extend away from the stroke core into the peri-infarct white matter. The amount of myelin loss exceeds axonal fiber loss in this peri-infarct region. Activation of microglia/macrophages takes place at 1 day after injection near injured axons. Neuronal tract tracing demonstrates that subcortical white matter stroke disconnects a large region of bilateral sensorimotor cortex. There is a robust glial response after stroke by BrdU pulse-labeling, and oligodendrocyte precursor cells are initiated to proliferate and differentiate within the first week of injury. These results demonstrate the utility of the endothelin-1 mediated subcortical stroke in the mouse to study post-stroke repair mechanisms, as the infarct core extends through the partially damaged peri-infarct white matter and induces an early glial progenitor response.

Abstract. Predators and parasites can control the abundance or biomass of herbivores with indirect effects on producer communities and ecosystems, but the interplay of multiple natural enemies may yield unexpected dynamics. We experimentally examined interactions between two microparasites (entomopathogenic nematodes) isolated from sandy grassland soils of coastal California: Heterorhabditis marelatus (Heterorhabditidae) and Steinernema feltiae (Steinernematidae). Heterorhabditis marelatus drives trophic cascades by attacking root-and stem-boring ghost moth caterpillars (Hepialus californicus, Hepialidae), thereby indirectly protecting bush lupine shrubs (Lupinus arboreus, Fabaceae). Extensive field surveys demonstrated sympatric overlap in microhabitat use under lupine canopies and similar mean prevalence of the two nematode species. Using a response-surface design in the laboratory, we varied relative and absolute microparasite densities to test for competitive outcomes within an evolutionary naı¨ve host, larvae of the greater wax moth Galleria mellonella (Pyralidae), and within the native host Hepialus californicus. Independent of conspecific or interspecific density, S. feltiae dominated as expected over H. marelatus within the naı¨ve Galleria, but S. feltiae infected hosts at low frequency and showed lower reproductive fitness than H. marelatus within native Hepialus hosts. Contrary to studies that demonstrate the pairwise dominance of steinernematid over heterorhabditid species in laboratory hosts, host resistance to S. feltiae may provide a mechanism for coexistence of multiple microparasite species. We hypothesize that the ubiquitous field prevalence and rapid life history of S. feltiae imply its use of widespread, abundant but small-bodied hosts and indicate the lack of direct competition with H. marelatus in the Hepialus-Lupinus trophic cascade.

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