Abstract: Non-invasive methods permitting accurate detection of innate immune dysfunction are critical to enhance the understanding, diagnosis, and treatment of inflammatory disorders. Identifying specific biomarkers of innate immune cells and their functional phenotypes, paired with subsequent PET tracer development, is thus an area of great interest with important implications for a broad range of diseases. However, existing targets lack cell specificity and/or fail to provide functionally relevant information regarding immune cell status. To overcome these limitations, a PET tracer was developed targeting TREM1 a highly specific biomarker of pro-inflammatory myeloid-driven immune responses.

Abstract: In aging mice, myeloid cell bioenergetics are suppressed in response to increased signaling by the lipid messenger prostaglandin E2 (PGE2), a major modulator of inflammation. In aging macrophages and microglia, PGE2 signaling through its EP2 receptor promotes the sequestration of glucose into glycogen, reducing glucose flux and mitochondrial respiration. Inhibition of myeloid EP2 signaling restores youthful energy metabolism in peripheral macrophages and microglia, rejuvenates systemic and brain inflammatory states, and prevents loss of hippocampal synaptic plasticity and spatial memory. Blockade of peripheral myeloid EP2 signaling is sufficient to restore cognition in aged mice.

Abstract: Aspects of the present invention include treating a subject having an acute of chronic central nervous system disorder, such as a brain disorder or spinal cord disorder, by administering an agent that inhibits TREM1 activity and/or expression.

Abstract: The present invention provides compositions and methods for treating an ischemic episode using misoprostol alone or in combination with anti-thrombotic agents.

Abstract: The present invention provides compositions and methods for treating an ischemic episode using misoprostol alone or in combination with anti-thrombotic agents.

Abstract: The present invention provides methods for attenuating neuronal inflammation and neuronal damage in case of acute or chronic injury of nerve cells of the central nervous system through prostaglandin E2 EP4 receptor activation. Methods for treating neuropathic pain are also provided.

Abstract: The present invention provides compositions and methods for treating an ischemic episode using PGE2 EP2 agonists and/or PGE2 EP4 agonists alone or in combination with anti-thrombotic agents.