NEW EFFECTIVE THERAPEUTIC APPROACHES TO CONTROL NEUROINFLAMMATION IMPROVE SEVERAL NEUROPATHOLOGIES

doi:10.4066/biomedicalresearch-C3-008

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

DOI: 10.4066/biomedicalresearch-C3-008

Abstract:

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 TNF�?±, IL-1�?², 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, D�?az 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 Parkinsonâ�?�?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.

Biography:

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