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Innate and adaptive immune responses Clinical Immunology: Principles and Practice. Chapter 3: Innate Immunity.  Rich  et al.
Martinon et al., 2009, Ann. Rev. Immunol. 27:229-265.
Duprez et al. Microbes & Infect. 11:1050
What Comprises the Innate Immune System in the CNS? Which CNS Cells Harbor Inflammasomes? What is the Regulation of the Innate Immune System After CNS Injury?
Primary  vs . secondary injury
SCI induces increased expression and processing of IL-1   and IL-18
SCI induces increased expression of Caspase-1, -11 and ASC
de Rivero Vaccari JP, Lotocki G, Marcillo AE, Dietrich WD, Keane RW. (2008). J Neurosci. 28: 3404-3414
Association of NLRP1 Proteins in Neurons
 
Keane et al., 2008
 
Confocal images of spinal cord sections demonstrating anti-ASC antibody penetration into spinal cord neurons de Rivero Vaccari JP, Lotocki G, Marcillo AE, Dietrich WD, Keane RW. (2008). J Neurosci. 28: 3404-3414
ASC neutralization blocks NALP1 inflammasome activity de Rivero Vaccari JP, Lotocki G, Marcillo AE, Dietrich WD, Keane RW. (2008). J Neurosci. 28: 3404-3414
ASC neutralization improves histopathological outcome and decreases spinal cord lesion volume de Rivero Vaccari JP, Lotocki G, Marcillo AE, Dietrich WD, Keane RW. (2008). J Neurosci. 28: 3404-3414
de Rivero Vaccari JP, Lotocki G, Marcillo AE, Dietrich WD, Keane RW. (2008). J Neurosci. 28: 3404-3414 Anti-ASC treatment improves functional outcomes after SCI
 
ASC neutralization decreases NLRP1 inflammasome activity
ASC neutralization improves histopathological outcomes after TBI
Conclusions ,[object Object],[object Object],[object Object]
 
High Extracellular K+ Activates Caspase-1  in Neuronal and Astrocytic Cultures
Extracellular ATP Activates Caspase-1  in Human Astrocytic Cultures
ATP-Induced Caspase-1 Activation is Blocked by  BBG and Probenecid
Pyroptosis is induced by the inflammasome, a multi-protein complex that stimulates  caspase-1 cleavage ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Poly(dA:dT) Induces a Dose-Dependent Innate Immune Response in Cortical Neurons ,[object Object],[object Object]
Poly(dA:dT) Increases Expression of AIM2 Inflammasome Components ,[object Object],[object Object]
Poly(dA:dT) Induces Assembly of the Pyroptosome and Subsequent Cell Death Cell Viability Assay  Oligomerization of ASC
Model of Neuronal Pyroptosis after CND Injury
Summary ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Dr. Juan Pablo de Rivero Vaccari Dr. Gerhard Dahl Dr. W. Dalton Dietrich Acknowledgments Julia Minkiewicz Stephanie Bacik

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