Electric stimulation of the vagus nerve reduced mouse neuroinflammation induced by lipopolysaccharide

G Meneses; M Bautista; A Florentino; G Díaz; G Acero; H Besedovsky; D Meneses; A Fleury; A Del Rey; G Gevorkian; G Fragoso; E Sciutto

doi:10.1186/s12950-016-0140-5

Electric stimulation of the vagus nerve reduced mouse neuroinflammation induced by lipopolysaccharide

J Inflamm (Lond). 2016 Oct 29:13:33. doi: 10.1186/s12950-016-0140-5. eCollection 2016.

Authors

G Meneses¹, M Bautista¹, A Florentino¹, G Díaz¹, G Acero¹, H Besedovsky², D Meneses³, A Fleury⁴, A Del Rey², G Gevorkian¹, G Fragoso¹, E Sciutto¹

Affiliations

¹ Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, AP 70228, Circuito Escolar S/N, Coyoacán, CP 04510 Ciudad de México Mexico.
² Institute of Physiology and Pathophysiology, Medical Faculty, Philipps University, Marburg, Germany.
³ Facultad Mexicana de Medicina, Universidad La Salle, Fuentes 17, Colonia, Tlalpan, Delegación Tlalpan, C.P. 14000 Ciudad de México Mexico.
⁴ Unidad Periférica, Instituto de Investigaciones Biomédicas, UNAM / Instituto Nacional de Neurología y Neurocirugía, Colonia la Fama, Delegación Tlalpan, Ciudad de México Mexico.

Abstract

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/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.

Keywords: Antiinflammatory; Lipopolysaccharide neuropathologies; Microglia; Neuroinflammation; Stimulation of vagus nerve.