CNS immune surveillance and neuroinflammation: endocannabinoids keep control.
To avoid inflammatory escalation, the central nervous system (CNS) harbors an impressive arsenal of cellular and molecular mechanisms enabling strict control of immune reactions. We here summarize studies suggesting that the old paradigm of the "CNS immune privilege" is overly simplistic. The immune system is allowed to keep the CNS under surveillance, but in a strictly controlled, limited and well-regulated manner. The first line of defense lies outside the brain parenchyma to spare neuronal tissue from the detrimental effects of an inflammatory immune response. As a second line of defense neuroinflammation is unavoidable when pathogens infiltrate the brain or the CNS-immune-homeostasis fails. Inflammation in the CNS is often accompanied by divers brain pathologies. We here review recent strategies to maintain brain homeostasis and modulate neuroinflammation. We focus on Multiple Sclerosis as an example of a complex neuroinflammatory disease. In the past years, several in vitro, in vivo and clinical studies suggested that the endocannabinoid system participates crucially in the immune control and protection of the CNS. We discuss here the endocannabinoid system as a key regulator mechanism of the cross talk between brain and the immune system as well as its potential as a therapeutic target.
Wolf
Susanne A
SA
Department of Cell- and Neurobiology, Institute of Anatomy, Faculty of Medicine, University of Zurich, Switzerland.
Tauber
Svantje
S
Ullrich
Oliver
O
D000818:Animals; D063385:Cannabinoid Receptor Modulators / Q000378:metabolism*; D002490:Central Nervous System / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D016503:Drug Delivery Systems; D063388:Endocannabinoids; D006801:Humans; D007107:Immune System / Q000378:metabolism; D007249:Inflammation / Q000188:drug therapy / Q000276:immunology* / Q000378:metabolism; D009103:Multiple Sclerosis / Q000188:drug therapy / Q000276:immunology / Q000503:physiopathology; D043882:Receptors, Cannabinoid / Q000276:immunology / Q000378:metabolism; D015398:Signal Transduction
D063385:Cannabinoid Receptor Modulators; D063388:Endocannabinoids; D043882:Receptors, Cannabinoid