Physiology Commons^™

Macrolide Derivatives Reduce Proinflammatory Macrophage Activation And Macrophage‐Mediated Neurotoxicity, Bei Zhang, Timothy J. Kopper, Xiaodong Liu, Zheng Cui, Steven G. Van Lanen, John C. Gensel

Physiology Faculty Publications

Introduction: Azithromycin (AZM) and other macrolide antibiotics are applied as immunomodulatory treatments for CNS disorders. The immunomodulatory and antibiotic properties of AZM are purportedly independent.

Aims: To improve the efficacy and reduce antibiotic resistance risk of AZM‐based therapies, we evaluated the immunomodulatory and neuroprotective properties of novel AZM derivatives. We semisynthetically prepared derivatives by altering sugar moieties established as important for inhibiting bacterial protein synthesis. Bone marrow‐derived macrophages (BMDMs) were stimulated in vitro with proinflammatory, M1, stimuli (LPS + INF‐gamma) with and without derivative costimulation. Pro‐ and anti‐inflammatory cytokine production, IL‐12 and IL‐10, respectively, was quantified using ELISA. Neuron culture …

Cerebrovascular Smooth Muscle Cells As The Drivers Of Intramural Periarterial Drainage Of The Brain, Roxana Aldea, Roy O. Weller, Donna M. Wilcock, Roxana O Carare, Giles Richardson

Physiology Faculty Publications

The human brain is the organ with the highest metabolic activity but it lacks a traditional lymphatic system responsible for clearing waste products. We have demonstrated that the basement membranes of cerebral capillaries and arteries represent the lymphatic pathways of the brain along which intramural periarterial drainage (IPAD) of soluble metabolites occurs. Failure of IPAD could explain the vascular deposition of the amyloid-beta protein as cerebral amyloid angiopathy (CAA), which is a key pathological feature of Alzheimer's disease. The underlying mechanisms of IPAD, including its motive force, have not been clarified, delaying successful therapies for CAA. Although arterial pulsations from …