Electric stimulation of the vagus nerve reduced mouse neuroinflammation induced by lipopolysaccharide
Por:
Meneses, G., Bautista, M., Florentino, A., Diaz, G., Acero, G., Besedovsky, H., Meneses, D., Fleury, A., Del Rey, A., Gevorkian, G., Fragoso, G., Sciutto, E.
Publicada:
29 oct 2016
Resumen:
Background: Neuroinflammation (NI) is a key feature in the pathogenesis
and progression of infectious and non-infectious neuropathologies, and
its amelioration usually improves the patient outcome. Peripheral
inflammation may promote NI through microglia and astrocytes activation,
an increased expression of inflammatory mediators and vascular
permeability that may lead to neurodegeneration. Several
anti-inflammatory strategies have been proposed to control peripheral
inflammation. Among them, electrical stimulation of the vagus nerve
(VNS) recently emerged as an alternative to effectively attenuate
peripheral inflammation in a variety of pathological conditions with few
side effects.
Considering that NI underlies several neurologic pathologies we explored
herein the possibility that electrically VNS can also exert
anti-inflammatory effects in the brain.
Methods: NI was experimentally induced by intraperitoneal injection of
bacterial lipopolysaccharide (LPS) in C57BL/6 male mice; VNS with
constant voltage (5 Hz, 0.75 mA, 2 ms) was applied for 30 s, 48 or 72 h
after lipopolysaccharide injection. Twenty four hours later, pro
inflammatory cytokines (IL beta 1, IL 6, TNF alpha) levels were measured
by ELISA in brain and spleen extracts and total brain cells were
isolated and microglia and macrophage proliferation and activation was
assessed by flow cytometry. The level of ionized calcium binding adaptor
molecule (Iba-1) and glial fibrillary acidic protein (GFAP) were
estimated in whole brain extracts and in histologic slides by Western
blot and immunohistochemistry, respectively.
Results: VNS significantly reduced the central levels of
pro-inflammatory cytokines and the percentage of microglia
(CD11b/CD45(low)) and macrophages (CD11b/CD45(high)), 24 h after the
electrical stimulus in LPS stimulated mice. A significantly reduced
level of Iba-1 expression was also observed in whole brain extracts and
in the hippocampus, suggesting a reduction in activated microglia.
Conclusions: VNS is a feasible therapeutic tool to attenuate the NI
reaction. Considering that NI accompanies different neuropathologies VNS
is a relevant alternative to modulate NI, of particular interest for
chronic neurological diseases.
Filiaciones:
Meneses, G.:
Univ Nacl Autonoma Mexico, Inst Invest Biomed, AP 70228,Circuito Escolar S-N, Coyoacan 04510, Ciudad De Mexic, Mexico
Bautista, M.:
Univ Nacl Autonoma Mexico, Inst Invest Biomed, AP 70228,Circuito Escolar S-N, Coyoacan 04510, Ciudad De Mexic, Mexico
Florentino, A.:
Univ Nacl Autonoma Mexico, Inst Invest Biomed, AP 70228,Circuito Escolar S-N, Coyoacan 04510, Ciudad De Mexic, Mexico
Diaz, G.:
Univ Nacl Autonoma Mexico, Inst Invest Biomed, AP 70228,Circuito Escolar S-N, Coyoacan 04510, Ciudad De Mexic, Mexico
Acero, G.:
Univ Nacl Autonoma Mexico, Inst Invest Biomed, AP 70228,Circuito Escolar S-N, Coyoacan 04510, Ciudad De Mexic, Mexico
Besedovsky, H.:
Univ Marburg, Inst Physiol & Pathophysiol, Fac Med, Marburg, Germany
Meneses, D.:
La Salle Univ, Fac Mexicana Med, Fuentes 17, Tlalpan 14000, Ciudad De Mexic, Mexico
Fleury, A.:
UNAM, Inst Nacl Neurol & Neurocirugia, Unidad Perifer, Inst Invest Biomed, Tlalpan, Ciudad De Mexic, Mexico
Del Rey, A.:
Univ Marburg, Inst Physiol & Pathophysiol, Fac Med, Marburg, Germany
Gevorkian, G.:
Univ Nacl Autonoma Mexico, Inst Invest Biomed, AP 70228,Circuito Escolar S-N, Coyoacan 04510, Ciudad De Mexic, Mexico
Fragoso, G.:
Univ Nacl Autonoma Mexico, Inst Invest Biomed, AP 70228,Circuito Escolar S-N, Coyoacan 04510, Ciudad De Mexic, Mexico
Sciutto, E.:
Univ Nacl Autonoma Mexico, Inst Invest Biomed, AP 70228,Circuito Escolar S-N, Coyoacan 04510, Ciudad De Mexic, Mexico
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