Zitnik R.J.,SetPoint Medical
Cleveland Clinic Journal of Medicine | Year: 2011
Implantable medical devices are finding increasing use in the treatment of diseases traditionally targeted with drugs. It is well established that the cholinergic antiinflammatory pathway serves as a physiological regulator of inflammatory responses, but stimulation of this pathway therapeutically by electrical stimulation of the vagus nerve can also diminish excessive or dysregulated states of inflammation. Recent data from a wide variety of animal models, as well as evidence of reduced vagal tone in rheumatoid arthritis and other inflammatory diseases, support the rationale for, and feasibility of, developing implantable vagal nerve stimulation devices to treat chronic inflammation in humans.
Lu B.,Central South University |
Lu B.,Feinstein Institute for Medical Research |
Kwan K.,Feinstein Institute for Medical Research |
Levine Y.A.,Feinstein Institute for Medical Research |
And 9 more authors.
Molecular Medicine | Year: 2014
The mammalian immune system and the nervous system coevolved under the influence of cellular and environmental stress. Cellular stress is associated with changes in immunity and activation of the NACHT, LRR and PYD domains-containing protein 3 (NLRP3) inflammasome, a key component of innate immunity. Here we show that α7 nicotinic acetylcholine receptor (α7 nAchR)- signaling inhibits inflammasome activation and prevents release of mitochondrial DNA, an NLRP3 ligand. Cholinergic receptor agonists or vagus nerve stimulation significantly inhibits inflammasome activation, whereas genetic deletion of α7 nAchR significantly enhances inflammasome activation. Acetylcholine accumulates in macrophage cytoplasm after adenosine triphosphate (ATP) stimulation in an α7 nAchR-independent manner. Acetylcholine significantly attenuated calcium or hydrogen oxide-induced mitochondrial damage and mitochondrial DNA release. Together, these findings reveal a novel neurotransmitter-mediated signaling pathway: acetylcholine translocates into the cytoplasm of immune cells during inflammation and inhibits NLRP3 inflammasome activation by preventing mitochondrial DNA release.
Olofsson P.S.,Feinstein Institute for Medical Research |
Rosas-Ballina M.,University of Basel |
Levine Y.A.,SetPoint Medical |
Tracey K.J.,Feinstein Institute for Medical Research
Immunological Reviews | Year: 2012
Neural reflex circuits regulate cytokine release to prevent potentially damaging inflammation and maintain homeostasis. In the inflammatory reflex, sensory input elicited by infection or injury travels through the afferent vagus nerve to integrative regions in the brainstem, and efferent nerves carry outbound signals that terminate in the spleen and other tissues. Neurotransmitters from peripheral autonomic nerves subsequently promote acetylcholine-release from a subset of CD4 + T cells that relay the neural signal to other immune cells, e.g. through activation of α7 nicotinic acetylcholine receptors on macrophages. Here, we review recent progress in the understanding of the inflammatory reflex and discuss potential therapeutic implications of current findings in this evolving field. © 2012 John Wiley & Sons A/S.
SetPoint Medical | Date: 2014-04-10
Devices, systems and methods for the treatment of chronic inflammatory disorders that include an implantable microstimulator and an external charger/controller wherein the controller is configured to operate using closed-loop feedback.
SetPoint Medical | Date: 2014-05-20
Medical devices, namely, devices used to treat chronic inflammatory and autoimmune disorders in the nature of neurostimulators which activate the bodys inflammatory reflex to reduce inflammation.