Premium
Baroreflex Activation Reduces Central Inflammation Induced by Lipopolysaccharide in Conscious Rats
Author(s) -
Brognara Fernanda,
Castania Jaci A.,
Lopes Alexandre H.,
Dias Daniel P. M.,
Cunha Thiago M.,
Cunha Fernando Q.,
Fazan Rubens,
Ulloa Luis,
Kanashiro Alexandre,
Salgado Helio Cesar
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.868.2
Subject(s) - lipopolysaccharide , inflammation , medicine , tumor necrosis factor alpha , saline , stimulation , baroreflex , endocrinology , anesthesia , blood pressure , pharmacology , chemistry , heart rate
Neuro‐immune interaction plays a significant role in the response of the organism to infection and inflammation. Our previous studies ( High Blood Pressure Research Scientific Sessions 2014 ) indicated that electrical stimulation of the aortic depressor nerve (ADNs), in conscious rats, modulates the innate inflammatory response to bacterial lipopolysaccharide (LPS). To expand the knowledge about the anti‐inflammatory potential of electrical stimulation of the baroreflex, in the current study we investigated the effect of ADNs in the experimental model of inflammation ‐ induced by LPS ‐ evaluating its impact on cytokines levels in the hypothalamus. Conscious rats were divided into six groups: I) Saline; II) LPS; III) LPS + bared wires electrodes without ADNs; IV) LPS + ADNs with bared wires electrodes without promoting hypotension; V) LPS + ADNs with bared wires electrodes promoting hypotension; VI) LPS + coated wires electrodes without ADNs. Under ketamine/xylazine anesthesia the subjects were implanted with a pair of bared wires, or coated wires with plastic, electrodes around the aortic depressor nerve and catheters were inserted into the left femoral artery and abdominal cavity, for arterial pressure (AP) recording and administration of LPS (5 mg/kg) or saline, respectively. On the next day, the AP was recorded while ADNs (0.5mA; 0.25ms; 15Hz) was performed during 10 minutes before and 10 minutes after the administration of LPS or saline. Ninety minutes post LPS the hypothalamus was collected to quantify the levels of tumor necrosis factor (TNF) and interleukin 6 (IL‐6). The results shown in the attached Figure demonstrate that ADNs prevented the increase of the hypothalamic levels of TNF and IL‐6 caused by LPS. In addition, ADNs without promoting hypotension or only the presence of bared wires electrodes in the aortic depressor nerve activated also the baroreflex, attenuating the hypothalamic levels of cytokines. In line with previous observations (Torres‐Rosas et al. Nature Medicine, 2014), no anti‐inflammatory effect was observed when the wires were coated, indicating a remarkable sensitivity of the ADN in the presence of bared wires electrodes even without external electrical stimulation. In conclusion, ADNs is a potential therapeutic target due to its preventive neuroprotective effect associated with the inhibition of central cytokines production. Thus, baroreflex electrical activation could be a novel strategy for treating inflammatory diseases involving the central nervous system, for instance, stroke, brain trauma, Parkinson's and Alzheimer's disease, and amyotrophic lateral sclerosis as well. Support or Funding Information FAPESP and CNPq. Baroreflex activation reduces central cytokines levels in response to LPSHypothalamic levels of tumor necrosis factor (TNF) and interleukin 6 (IL‐6) 90 minutes after the administration of saline, or LPS combined, or not, with electrical stimulation of the aortic depressor nerve (ADNs). Bars represent mean ± standard error. * P < 0.05.