NEW EFFECTIVE THERAPEUTIC APPROACHES TO CONTROL NEUROINFLAMMATION IMPROVE SEVERAL NEUROPATHOLOGIES
Joint Event on International Conference on CELL AND GENE THERAPY & World Congress on CLINICAL AND MEDICAL MICROBIOLOGY
September 10- 11 , 2018 | Dublin , Ireland
Meneses G, Rassy D, Espinoza A, Esteban Ponciano J A, Perez-Osorio N, Barcenas B, Olvera M, Besedovsky H, Fragoso G and Sciutto E
UNAM, Mexico Philipps University, Germany
Posters & Accepted Abstracts : Biomed Res
Statement of the Problem: Even though acute, transient neuroinflammation (NI) is a beneficial defensive response to harmful stimuli, sustained NI can lead to pathological conditions. NI is a common trait in many infectious and non-infectious neurological diseases and may promote their onset and progression. Its role in sepsis, Parkinson disease, stroke, and multiple sclerosis places NI as a new common therapeutic target. Controlling subacute and chronic NI may help to restore CNS physiology and homeostasis; however, NI is currently treated only during multiple sclerosis crises, being unattended in other diseases. The absence of an adequate anti-inflammatory response may explain the scarce research on this approach. Methodology & Theoretical Orientation: The potential of electric stimulation of the vagus nerve (ESVN) and intranasal administration of glucocorticoids were studied in models of sepsis (LPS-treated mice), Parkinson disease (induced by 1-methyl-4-phenyl- 1,2,3,6-tetrahydropyridine, MPTP), ischemic stroke (induced by middle cerebral artery occlusion, MCAO), and multiple sclerosis (autoimmune encephalomyelitis elicited by the myelin oligodendrocyte glycoprotein peptide 35-55). Findings: Both ESVN and intranasal steroid administration effectively reduced central levels of TNFα, IL-1β, and IL6 (measured by ELISA) and the percentage of CD11b+/CD45 macrophages/microglial cells (measured by FACS). ESVN also reduced the expression of Iba-1 in the cortex and hippocampus. ESVN reduced astrocyte activation (GFAP) and restored the expression of tyrosinehydroxylase (TH)-positive neurons in the substantia nigra pars compacta (SNc). Intranasal administration of dexamethasone significantly reduced mortality in the stroke model. Moreover, intranasally-treated mice exhibited lower morbidity and central inflammation, and a reduced size of the ischemic lesions. In multiple sclerosis, the intranasal route was more effective than intravenous in improving EAE-associated morbidity. Conclusion & Significance: Our results highlight the possibility of reducing NI in several neuropathologies, restoring homeostasis more efficiently than current treatments. Recent Publications 1. Meneses G, Bautista M, Florentino A, Díaz G, Acero G, Besedovsky H, Meneses D, Fleury A, Del Rey A, Gevorkian G, Fragoso G, Sciutto E (2016). Electric stimulation of the vagus nerve reduced mouse neuroinflammation induced by lipopolysaccharide. J Inflamm (Lond). 13: 33. 2. Jackson-Lewis V, Lester D, Kozina E, Przedborski S, Smeyne RJ (2015). From man to mouse: the MPTP model of Parkinson’s disease. In: LeDoux M, editor. Movement disorders: genetics and models. 2nd ed. Amsterdam: Elsevier. DOI: 10.1016/ B978-0-12-405195-9.00017-2. 3. Bittner S, Afzali AM, Wiendl H, Meuth SG (2014). Myelin oligodendrocyte glycoprotein (MOG35-55) induced experimental autoimmune encephalomyelitis (EAE) in C57BL/6 mice. J Vis Exp. (86): 51275.