https://eutils.ncbi.nlm.nih.gov/entrez/eutils/efetch.fcgi?db=pubmed&id=22818207&retmode=xml&tool=Litmetric&email=readroberts32@gmail.com&api_key=61f08fa0b96a73de8c900d749fcb997acc09 228182072013011720240418
1742-209492012Jul20Journal of neuroinflammationJ NeuroinflammationAcute injury in the peripheral nervous system triggers an alternative macrophage response.17617610.1186/1742-2094-9-176The activation of the immune system in neurodegeneration has detrimental as well as beneficial effects. Which aspects of this immune response aggravate the neurodegenerative breakdown and which stimulate regeneration remains an open question. To unravel the neuroprotective aspects of the immune system we focused on a model of acute peripheral nerve injury, in which the immune system was shown to be protective.To determine the type of immune response triggered after axotomy of the sciatic nerve, a model for Wallerian degeneration in the peripheral nervous system, we evaluated markers representing the two extremes of a type I and type II immune response (classical vs. alternative) using real-time quantitative polymerase chain reaction (RT-qPCR), western blot, and immunohistochemistry.Our results showed that acute peripheral nerve injury triggers an anti-inflammatory and immunosuppressive response, rather than a pro-inflammatory response. This was reflected by the complete absence of classical macrophage markers (iNOS, IFN γ, and IL12p40), and the strong up-regulation of tissue repair markers (arginase-1, Ym1, and Trem2). The signal favoring the alternative macrophage environment was induced immediately after nerve damage and appeared to be established within the nerve, well before the infiltration of macrophages. In addition, negative regulators of the innate immune response, as well as the anti-inflammatory cytokine IL-10 were induced. The strict regulation of the immune system dampens the potential tissue damaging effects of an over-activated response.We here demonstrate that acute peripheral nerve injury triggers an inherent protective environment by inducing the M2 phenotype of macrophages and the expression of arginase-1. We believe that the M2 phenotype, associated with a sterile inflammatory response and tissue repair, might explain their neuroprotective capacity. As such, shifting the neurodegeneration-induced immune responses towards an M2/Th2 response could be an important therapeutic strategy.YdensElkeEPeripheral Neuropathy Group, Department of Molecular Genetics, VIB and University of Antwerp, Antwerpen, Belgium.CauwelsAnjeAAsselberghBobBGoethalsSofieSPeeraerLieveLLornetGuillaumeGAlmeida-SouzaLeonardoLVan GinderachterJo AJATimmermanVincentVJanssensSophieSengJournal ArticleResearch Support, Non-U.S. Gov't20120720
EnglandJ Neuroinflammation1012229741742-2094IMAcute DiseaseAnimalsImmunity, CellularimmunologyMacrophagesimmunologypathologyMiceMice, Inbred C57BLPeripheral Nerve InjuriesimmunologypathologyPeripheral Nervous SystemimmunologypathologyWallerian Degenerationimmunologypathology201231520127202012724602012724602013118602012720epublish22818207PMC341908410.1186/1742-2094-9-1761742-2094-9-176Waller A. Experiments on the section of the glossopharyngeal and hypoglossal nerves of the frog, and observations of the alterations produced thereby in the structure of their primitive fibres. Phil Transact Royal Soc London. 1850;140:423–429. doi: 10.1098/rstl.1850.0021.10.1098/rstl.1850.00210Saxena S, Caroni P. Mechanisms of axon degeneration: from development to disease. Prog Neurobiol. 2007;83:174–191. doi: 10.1016/j.pneurobio.2007.07.007.10.1016/j.pneurobio.2007.07.00717822833Shamash S, Reichert F, Rotshenker S. 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