Purinergic Receptor Stimulation Reduces Cytotoxic Edema and Brain Infarcts in Mouse Induced by Photothrombosis by Energizing Glial Mitochondria

Treatments to improve the neurological outcome of edema and cerebral ischemic stroke are severely limited. Here, we present the first in vivo single cell images of cortical mouse astrocytes documenting the impact of single vessel photothrombosis on cytotoxic edema and cerebral infarcts. The volume of astrocytes expressing green fluorescent protein (GFP) increased by over 600% within 3 hours of ischemia. The subsequent growth of cerebral infarcts was easily followed as the loss of GFP fluorescence as astrocytes lysed. Cytotoxic edema and the magnitude of ischemic lesions were significantly reduced by treatment with the purinergic ligand 2-methylthioladenosine 5′ diphosphate (2-MeSADP), an agonist with high specificity for the purinergic receptor type 1 isoform (P2Y1R). At 24 hours, cytotoxic edema in astrocytes was still apparent at the penumbra and preceded the cell lysis that defined the infarct. Delayed 2MeSADP treatment, 24 hours after the initial thrombosis, also significantly reduced cytotoxic edema and the continued growth of the brain infarction. Pharmacological and genetic evidence are presented indicating that 2MeSADP protection is mediated by enhanced astrocyte mitochondrial metabolism via increased inositol trisphosphate (IP3)-dependent Ca2+ release. We suggest that mitochondria play a critical role in astrocyte energy metabolism in the penumbra of ischemic lesions, where low ATP levels are widely accepted to be responsible for cytotoxic edema. Enhancement of this energy source could have similar protective benefits for a wide range of brain injuries

New Strategies for Public Pay: Rethinking Government Compensation Programs

Chapter contribution, \u27Job Classification\u27 by Lyn M. Holley and J. R. O\u27Connell in Howard Risher & Charles H. Fay (Eds.), New strategies for public pay: Rethinking government compensation programs (pp. 76-97). San Francisco: Jossey-Bass. The survival and success of public organizations depends on employee satisfaction and motivation to improve performance. New Strategies for Public Pay addresses one of the strongest motivators?compensation. The book outlines proven strategies, many of which are successfully used in private industry, that are also well-suited for government organizations. Specific programs are described and analyzed by experts from government, academia, think tanks, labor unions, and private business, running the gamut from merit pay to competency-based pay to gainsharing.New Strategies for Public Pay introduces a range of alternative pay systems that show public sector managers how they can:? Set standards that match the unique needs of individual organizations? Stimulate desired new behaviors necessary to overcome the fear of change and business as usual mentality? Energize employees and provide a fresh incentive for continuing improved performanceThe decision whether or not to revolutionize pay systems is fundamental. The way compensation is addressed and managed can either hinder or help accomplish an organization\u27s mission. New Strategies for Public Pay offers a useful framework for planning compensation programs that are in line with the times and that will help create more efficient, flexible, and responsive public organizations.https://digitalcommons.unomaha.edu/gertontology_books/1001/thumbnail.jp