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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) 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.
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http://dx.doi.org/10.1186/s12974-019-1512-6 | DOI Listing |
J Neurosci Methods
October 2025
Department of Physiology and Aging, College of Medicine, University of Florida, Gainesville, FL 32611, USA; Center for Integrative Cardiovascular and Metabolic Diseases, University of Florida, Gainesville, FL 32611, USA; Center for Smell and Taste, University of Florida, Gainesville, FL 32611, USA;
Background: Arterial baroreceptors are mechanosensitive nerve endings that detect blood pressure deviations and transmit this information to the central nervous system via vagal afferent neurons. Vagal afferent neuron cell bodies reside in the nodose ganglion (NG) and they terminate in the nucleus of the solitary tract (NTS) within the brainstem, thus serving as a critical component of the baroreflex circuitry. We previously found that specific angiotensin-sensitive vagal afferent nerve terminals within the NTS (referred to as NTS afferents) are sufficient to initiate baroreflex responses in both normotensive and hypertensive conditions.
View Article and Find Full Text PDFAntioxidants (Basel)
June 2025
Instituto de Ciencias Biomédicas, Facultad de Ciencias de la Salud, Universidad Autónoma de Chile, Santiago 8910060, Chile.
The carotid body (CB) senses arterial PO, PCO, and pH levels, eliciting reflex responses to maintain cardiorespiratory homeostasis. Chronic intermittent hypoxia (CIH), the hallmark of obstructive sleep apnea, elicits autonomic and cardiorespiratory alterations that are attributed to an enhanced CB chemosensory responsiveness to hypoxia, which in turn activates neurons and glial cells in the nucleus of the tractus solitarius (NTS). Although the CB contribution to the CIH-induced pathological alterations is well-known, the underlying mechanisms are not fully understood.
View Article and Find Full Text PDFAlzheimers Dement (N Y)
June 2025
Research Cognition Therapeutics Pittsburgh Pennsylvania USA.
Introduction: CT1812 (zervimesine) is an orally dosed modulator of the sigma-2 receptor (S2R) currently in clinical development for the treatment of Alzheimer's disease (AD). CT1812 has been shown in preclinical and early clinical trials to selectively prevent and displace binding of amyloid beta oligomers from their synaptic receptors and has improved cognitive function in animal models of AD.
Methods: SEQUEL (NCT04735536) is a completed Phase 2, randomized, placebo-controlled 4-week crossover trial in adults with mild-to-moderate AD that investigated the effect of CT1812 on safety, synaptic function using quantitative electroencephalography (qEEG), and biomarkers.
Food Funct
July 2025
College of Food Science and Engineering, Northwest A&F University, Yangling 712100, China.
Alzheimer's disease (AD) is mainly manifested by cognitive dysfunction, accompanied by excessive β-amyloid (Aβ) deposition and neuroinflammation. The regulation of vagus nerve (VN) signal transmission is crucial for influencing the pathological progression of AD and exploring new therapeutic approaches. Two doses of 2'-fucosyllactose (2'-FL, 500 and 1000 mg kg) were administered orally to AD model mice.
View Article and Find Full Text PDFPharmaceuticals (Basel)
March 2025
Department of Pharmacology and Toxicology, Faculty of Pharmacy, Alexandria University, Alexandria 21511, Egypt.
: Sepsis has been shown to depress arterial baroreceptor function, and this effect is counterbalanced by the cholinergic anti-inflammatory pathway. Considering the importance of central adenosine receptors in baroreceptor function, this study tested whether central adenosine A3 receptors (A3ARs) modulate the cholinergic-baroreflex interaction in sepsis and whether this interaction is modulated by mitogen-activated protein kinases (MAPKs) and related proinflammatory cytokines. : Sepsis was induced by cecal ligation and puncture (CLP) and rats were instrumented with femoral and intracisternal (i.
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