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Page 31
Cell and Gene Therapy 2018 & Clinical Microbiology Congress 2018
Biomedical Research
|
ISSN: 0976-1683
|
Volume 29
S e p t e m b e r 1 0 - 1 1 , 2 0 1 8 | D u b l i n , I r e l a n d
allied
academies
Joint Event on
CLINICAL AND MEDICAL MICROBIOLOGY
CELL AND GENE THERAPY
&
World Congress on
International Conference on
Biomed Res 2018, Volume 29 | DOI: 10.4066/biomedicalresearch-C3-008
NEW EFFECTIVE THERAPEUTIC APPROACHES TO CONTROL
NEUROINFLAMMATION IMPROVE SEVERAL NEUROPATHOLOGIES
Meneses G
1
, Rassy D
1
, Espinoza A
1
, Esteban
Ponciano J A
1
, Perez-Osorio N
1
, Bárcenas B
1
,
Olvera M
1
, Besedovsky H
2
, Fragoso G
1
and
Sciutto E
1
1
UNAM, Mexico
2
Philipps University, Germany
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 tyrosine-
hydroxylase (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.