Activation of innate immunity in the CNS triggers neurodegeneration through a Toll-like receptor 4-dependent pathway

By S. Lehnardt, L. Massillon, Pamela L. Follett, F. Jensen, R. Ratan, P. Rosenberg, Joseph J. Volpe, T. Vartanian. Proceedings of the National Academy of Sciences of the United States of America, 2003

1,054 citations recorded by the source corpus.

Subfields: Immunology, Neurology

View Paper: https://www.semanticscholar.org/paper/88f57ae9754eef664a66d073e7b8ba4f5a879a2f

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Immunology

1. S. Rivest
2. M. Block
3. T. Wyss‐Coray
4. Kaoru Saijo
5. Jau-Shyong Hong
6. Guo-Yuan Yang
7. O. Levy
8. J. Rogers

In Neurology

1. M. Block
2. Jau-Shyong Hong
3. S. Lehnardt
4. S. Rivest
5. T. Wyss‐Coray
6. Guo-Yuan Yang
7. J. Rogers
8. J. Collier

Citations in the corpus

• Regulation of innate immune responses in the brain (2009, background): “Although a single injection of LPS is probably not sufficient to cause neurodegeneration, long-term exposure to PAMPs, as occurs during severe meningitis for example, has profound effects on the nervous tissu”
• The biphasic function of microglia in ischemic stroke (2017, positive): “…Toll-like receptor 2 (TLR2) and Toll-like receptor 4 (TLR4) activated microglia, mediated pro-inflammatory cytokine production, and caused brain damage after focal cerebral ischemia (Caso et al., 2007; Kilic et al., 2008; Lehnardt et al., 2003, 2007; Rosenberger et al., 2014; Yenari et al., 2010).”
• Microglia and inflammation-mediated neurodegeneration: multiple triggers with a common mechanism. (2005, background): “However, neonatal microglial activation has also been linked with the amplification of neurotoxicity, where systemic neonatal exposure to LPS has been shown to significantly amplify neuronal death associated with ischemic insult (Lehnardt et al., 2003).”
• Systemic LPS causes chronic neuroinflammation and progressive neurodegeneration (2007, background): “Systemic exposure to LPS in the neonate was also shown to significantly amplify neuronal death associated with ischemic insult (Lehnardt et al., 2003).”
• Inflammation in Alzheimer disease-a brief review of the basic science and clinical literature. (2012, background): “CNS microinjections of the TLR 2 or 4 ligands zymosan and lipopolysaccharide (LPS), respectively, cause robust glial activation and elicit substantial neurodegeneration (Popovich et al. 2002; Lehnardt et al. 2003).”
• Identification of miRNA Changes in Alzheimer's Disease Brain and CSF Yields Putative Biomarkers and Insights into Disease Pathways (2008, positive): “TLR signaling is implicated in activation of microglia that aid in the phagocytic clearance of A β fibrils as well as increased neurodegeneration in animal models of AD [33,39,63].”
• The inflammatory response in stroke. (2007, background): “Furthermore, work in neonatal mice indicated that TLR4 was necessary for microglial activation following hypoxia/ischemia (Lehnardt et al., 2003).”
• Microglia-mediated neurotoxicity: uncovering the molecular mechanisms (2007, background): “, and is reported to be a crucial contributor to the microglial response to LP”
• Immune activation in brain aging and neurodegeneration: too much or too little? (2009, background): “Indeed, CNS microinjections of the TLR 2 or 4 ligands zymosan and LPS, respectively, cause robust glial activation and elicit substantial neurodegeneration (Lehnardt et al., 2003; Popovich et al., 2002).”
• Innate immunity of the newborn: basic mechanisms and clinical correlates (2007, background): “In addition, emerging evidence indicates that TLR-mediated pro-inflammatory cytokine induction by microglia might contribute to central nervous system damage in pre-term newborns that can culminate in cerebral palsy”