[en] It is now well accepted that inflammatory responses in brain contribute to the genesis and evolution of damage in neurological diseases, trauma, and infection. Inflammatory mediators including cytokines, cell adhesion molecules, and reactive oxygen species including NO are detected in human brain and its animal models, and interventions that reduce levels or expression of these agents provide therapeutic benefit in many cases. Although in some cases, the causes of central inflammatory responses are clear--for example those due to viral infection in AIDS dementia, or those due to the secretion of proinflammatory substances by activated lymphocytes in multiple sclerosis--in other conditions the factors that allow the initiation of brain inflammation are not well understood; nor is it well known why brain inflammatory activation is not as well restricted as it is in the periphery. The concept is emerging that perturbation of endogenous regulatory mechanisms could be an important factor for initiation, maintenance, and lack of resolution of brain inflammation. Conversely, activation of intrinsic regulatory neuronal pathways could provide protection in neuroinflammatory conditions. This concept is the extension of the principle of "central neurogenic neuroprotection" formulated by Donald Reis and colleagues, which contends the existence of neuronal circuits that protect the brain against the damage initiated by excitotoxic injury. In this paper we will review work initiated in the Reis laboratory establishing that activation of endogenous neural circuits can exert anti-inflammatory actions in brain, present data suggesting that these effects could be mediated by noradrenaline, and summarize recent studies suggesting that loss of noradrenergic locus ceruleus neurons contributes to inflammatory activation in Alzheimer's disease.
Disciplines :
Neurology
Author, co-author :
Galea, Elena; Department of Anesthesiology, University of Illinois, Chicago, Illinois, USA
HENEKA, Michael ; Department of Neurology, University of Bonn, Bonn, Germany
Dello Russo, Cinzia; Department of Anesthesiology, University of Illinois, Chicago, IL, United States
Feinstein, Douglas L; Department of Anesthesiology, University of Illinois, Chicago, IL, United States ; MC 519, Chicago, IL 60612, United States
External co-authors :
yes
Language :
English
Title :
Intrinsic regulation of brain inflammatory responses.
Publication date :
October 2003
Journal title :
Cellular and Molecular Neurobiology
ISSN :
0272-4340
eISSN :
1573-6830
Publisher :
Kluwer Academic/Plenum Publishers, New York, Us ny
Volume :
23
Issue :
4-5
Pages :
625 - 635
Peer reviewed :
Peer Reviewed verified by ORBi
Funding text :
We thank Liubov Lyandvert for excellent technical assistance for studies carried out in the Don Reis laboratory, and Anthony Sharp and Patricia Murphy for assistance with studies carried out at UIC. We thank Irina Balyasnikova for studies of brain endothelial cells. This work was supported by grants from the National Multiple Sclerosis Society, the N.I.H., the VA research division, and the American Heart Association.
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