Neurological Disorders: Resistance to Neurodegeneration
This is a general model of brain trauma, including cerebral ischemia and head injury. It addresses the sequelae to any insult to neurons. These include the reaction of the neurons themselves, but also the supporting glia, microglia (the brain's immune system), and peripheral inflammatory reactions that may impinge on the brain. These reactions are perhaps most relevant to head injury trauma. The brain irradiation challenge assay represents a significant improvement over other first-pass assays for looking at resistance or susceptibility to neuronal degeneration. This is both because it is an in vivo assay in adults, with physiological relevance in contrast to the various experimental insults that can be performed in vitro, and also because it can evaluate the overall system response to insult, including the impact of glial cells, vasculature, immune response, and the response of neuronal cells per se.
Mice are received 3-4 weeks after having recovered from 500 rad whole body gamma irradiation. They are then exposed to another 500 rad (head exposure only though) on day 1 and day 4 and then euthanized on day 7 and brains are harvested. The number of Ki67 immunopositive cells in the left and right dentate gyrus of one to two 5 μm paraffin sections of brain are counted and averaged to represent the survival of new neurons to the radiation challenge. A phenotype with a greater number of Ki67 positive neurons would suggest that inhibiting the gene results in increased resistance to neurodegeneration.
Displayed to below is a sample graph of how neurodegenerative observations are presented. In comprehensive phenotypic data packages graphs are interactive. Raw or calculated data and statistics can be seen by clicking on points in the graph.
Figure illustrates number of Ki67 immunoreactive cells in mutant mice. Number of Ki67 positive cells for wild type littermates (green circle), homozygous (red diamond), and recent historical wild types (purple line) are plotted against long-term historical values (± 2 standard deviations) for wild type animals (green shading). Recent wild type values are calculated from data collected within 60 days of current measures and long-term historical values are derived from data collected on more than 10,000 wild type mice.