Neuroinflammation

Sorting the Axon toWrap Signaling in Both Parties 

The ratio of the axonal diameter divided by the diameter of the axon plus its myelin sheath is referred to as the G-ratio. Usually, the G-ratio is maintained betw een 0.6 and 0.7. The importance of this constancy lays in the fact that thickness of myelin w raps depend on axonal thickness and demonstrate propor-tionahty. One of the main regulators of the myelin thickness is signal(s) induced by Neuregulin-ErbB system (Michailov et al., 2004). Adchtionally, neurotrophins likeBDNF andneu-rotrophin p75 are also thought to be involved in regulating myelin sheath thickness (Tolw ani et al., 2004). 

Although inflammation is a self-defense operation, it may attain harmful proportions if not controlled strictly. Evolved as much as W e are, human inflammatory system still gets into the overdrive mode in several instances and instead of being efficacious, creates havoc. Neuroinflammation is one such example. Unrestricted inflammatory response in CNS is now considered a root cause of several neurodegenerative diseases, as an overdose of inflammatory moieties tend to injure/ kill neurons. 

On the other hand, extrinsic stimuh are often delivered by viruses and bacteria. Bacterial products like lipopolysac-charide (LPS) and DNA with motifs of unmethylated CpG cUnucleotides are extremely potent inducers of neuroinflammation. AdcUtionally, viruses themselves, or their products like retroviral coat protein gp4l and gpl20, double stranded RNA, and transcription factors hke Tat, also induce inflammatory responses in brain cells. 

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Key Words Chemokine receptors CNS multiple sclerosis microglia NK cells EAE fractalkine neuroinflammation. 

John A. Belperio Department of Medicine, Division of Pulmonary and Critical Care Medicine, David Geffen School of Medicine at University of California at Los Angeles, Los Angeles, CA, USA Christopher C. Broder Department of Microbiology and Immunology, Uniformed Services University, Bethesda, MD, USA Astrid E. Cardona Neuroinflammation Research Center, Department of Neurosciences, Lerner Research Institute, Cleveland Clinic, Cleveland,... 

Richard M. Ransohoff Neuroinflammation Research Center, Department of Neurosciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA... 

Fractalkine-CX3R1 actions in microglia and NK cells during neuroinflammation. 

Fig. 17.2. Fractalkine-CX3CR1 actions in microglia and NK cells during neuroinflammation. Fractalkine and CX3CR1 provide key regulatory input for microglia and NK cells, the fractalkine-responsive cell types implicated in EAE. In particular, fractalkine and CX3CR1 mediate tonic inhibition of deleterious microglial activation, and recruit regulatory NK cells to the inflamed CNS during EAE.

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