Electric stimulation of the vagus nerve reduced mouse neuroinflammation induced by lipopolysaccharide.
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-1β, IL-6, TNFα) 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/CD45low) and macrophages (CD11b/CD45high), 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.
Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, AP 70228, Circuito Escolar S/N, Coyoacán, CP 04510 Ciudad de México Mexico.
G
G
Meneses
Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, AP 70228, Circuito Escolar S/N, Coyoacán, CP 04510 Ciudad de México Mexico.
M
M
Bautista
Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, AP 70228, Circuito Escolar S/N, Coyoacán, CP 04510 Ciudad de México Mexico.
A
A
Florentino
Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, AP 70228, Circuito Escolar S/N, Coyoacán, CP 04510 Ciudad de México Mexico.
G
G
Díaz
Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, AP 70228, Circuito Escolar S/N, Coyoacán, CP 04510 Ciudad de México Mexico.
G
G
Acero
Institute of Physiology and Pathophysiology, Medical Faculty, Philipps University, Marburg, Germany.
H
H
Besedovsky
Facultad Mexicana de Medicina, Universidad La Salle, Fuentes 17, Colonia, Tlalpan, Delegación Tlalpan, C.P. 14000 Ciudad de México Mexico.
D
D
Meneses
Unidad Periférica, Instituto de Investigaciones Biomédicas, UNAM / Instituto Nacional de Neurología y Neurocirugía, Colonia la Fama, Delegación Tlalpan, Ciudad de México Mexico.
A
A
Fleury
Institute of Physiology and Pathophysiology, Medical Faculty, Philipps University, Marburg, Germany.
A
A
Del Rey
Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, AP 70228, Circuito Escolar S/N, Coyoacán, CP 04510 Ciudad de México Mexico.
G
G
Gevorkian
Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, AP 70228, Circuito Escolar S/N, Coyoacán, CP 04510 Ciudad de México Mexico.
G
G
Fragoso
Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, AP 70228, Circuito Escolar S/N, Coyoacán, CP 04510 Ciudad de México Mexico.
E
E
Sciutto
Antiinflammatory; Lipopolysaccharide neuropathologies; Microglia; Neuroinflammation; Stimulation of vagus nerve