Neuroinflammation in the NTS is associated with changes in cardiovascular reflexes during systemic inflammation

Abstract

Background Lipopolysaccharide (LPS)-induced systemic inflammation (SI) is associated with neuroinflammation in the brain, hypotension, tachycardia, and multiple organs dysfunctions. Considering that during SI these important cardiovascular and inflammatory changes take place, we measured the sensitivity of the cardiovascular reflexes baroreflex, chemoreflex, and Bezold-Jarisch that are key regulators of hemodynamic function. We also evaluated neuroinflammation in the nucleus tractus solitarius (NTS), the first synaptic station that integrates peripheral signals arising from the cardiovascular and inflammatory status. Methods We combined cardiovascular recordings, immunofluorescence, and assays of inflammatory markers in male Wistar rats that receive iv administration of LPS (1.5 or 2.5 mg kg −1 ) to investigate putative interactions of the neuroinflammation in the NTS and in the anteroventral preoptic region of the hypothalamus (AVPO) with the short-term regulation of blood pressure and heart rate. Results LPS induced hypotension, tachycardia, autonomic disbalance, hypothermia followed by fever, and reduction in spontaneous baroreflex gain. On the other hand, during SI, the bradycardic component of Bezold-Jarisch and chemoreflex activation was increased. These changes were associated with a higher number of activated microglia and interleukin (IL)-1β levels in the NTS. Conclusions The present data are consistent with the notion that during SI and neuroinflammation in the NTS, rats have a reduced baroreflex gain, combined with an enhancement of the bradycardic component of Bezold-Jarisch and chemoreflex despite the important cardiovascular impairments (hypotension and tachycardia). These changes in the cardiac component of Bezold-Jarisch and chemoreflex may be beneficial during SI and indicate that the improvement of theses reflexes responsiveness though specific nerve stimulations may be useful in the management of sepsis.

Baroreceptor denervation reduces inflammatory status and worsens cardiovascular collapse during systemic inflammation

“…In the search for mechanisms underlying hemodynamic control during SI, we used spectral analysis of PI in the frequency domain, which showed that HF component of PI was significantly reduced at 3 hours after endotoxin in Control + LPS and in SAD + LPS in relation to Control + Sal (Fig 3 A and D). These observations are in line with the concept that LPS-induced tachycardia is triggered by mechanisms resulting in a decrease of vagal modulation to the heart (18). Significant changes in the autonomic control to the heart have been observed during the initial phase of sepsis-associated SI as a compensatory adjustment to avoid circulatory shock (29).…”

“…Considering our previous study that documented hemodynamic and inflammatory changes 3 hours following LPS administration (18), cytokine levels were evaluated at this same period in plasma and spleen as an index of SI and the modulatory role of sino-aortic afferents on the splenic anti-inflammatory reflex, respectively.…”

“…Considering previous studies (17,18,33) and our own data (Fig. 1) documenting cardiovascular collapse during SI, we further evaluated the vascular function after LPS administration in Control and SAD animals in mesenteric resistance arteries.…”

“…Baroreceptors afferents integrity is mandatory in the control of blood pressure within a narrow range of variation and surgically removed baroreceptors afferents rats [sino-aortic denervation (SAD)] had higher variability of the mean arterial pressure (11,13,14). More recently, it has been shown the role of baroreceptor afferents mediating LPS-induced cardiovascular collapse (15–18). Moreover, in SI, electrical baroreflex stimulation in rats has been reported to blunt LPS-induced production of cytokines in the hypothalamus (19), indicating an anti-inflammatory role played by aortic depressor nerve stimulation.…”

Downregulation of Long Noncoding RNA TUG1 Attenuate MTDH /NF-κB/IL-1β mediated inflammatory damage via Targeting miR-29b-1-5p After Spinal cord ischemia reperfusion in rats

“…The in situ expression of MTDH and the astrocytic marker GFAP was analyzed as described previously [27]. The fixed spinal cord was sectioned into 10 mm-thick slices, and probed with rabbit anti-MTDH (1:100, Proteintech), rabbit anti-GFAP (1:800, ServiceBio) and rabbit anti-DAPI (1:800, ServiceBio) primary antibodies, followed by Cy3-labeled goat anti-rabbit IgG secondary antibody (1:500, ServiceBio).…”