Juan Zhou

Infrasound, a low-frequency physical stimulus from environmental and anthropogenic sources, is assumed to impact microvascular regulation, though the mechanism is not fully understood. This study examines the effects of bipolar infrasound exposure (1 Hz, 100 dB) on the sublingual microcirculation in mice, with a single 4-hour exposure and repeated 4-hour daily exposures for 14 days. Control mice were placed in the same chamber without infrasound exposure. Using sidestream dark-field (SDF) videomicroscopy and laser Doppler flowmetry (LDF), we assessed microvascular diameter oscillations (vasomotion) and flow changes (flowmotion), respectively. A single exposure significantly increased vasomotion oscillation amplitude in the low-frequency band, while changes in the very-low- and high-frequency bands were not significant. Flowmotion measured by LDF significantly increased in the very-low-frequency band after a single exposure, while the other frequency bands remained unchanged. In contrast, repeated exposure significantly increased vasomotion oscillation amplitude within the very-low-, low-, and high-frequency bands, while LDF-derived flowmotion did not change significantly. The findings suggest that repeated exposure to infrasound may induce irregular microvascular oscillations, primarily affecting vessel diameter rather than overall perfusion, warranting further exploration into related mechanisms.

Ischemic stroke triggers neuroinflammation that can drive CNS injury-induced immunodepression syndrome (CIDS), a peripheral immunosuppressive state associated with increased infection risk. The endocannabinoid system, particularly cannabinoid receptor type 2 (CB2), represents a promising immunomodulatory target because of its anti-inflammatory actions and limited psychoactive liability. In this study, we investigated whether CB2 receptor activation confers neuroprotection and preserves systemic immune responsiveness in a murine photothrombotic stroke (PTS) model. Male C57BL/6 mice underwent PTS or sham surgery and were treated before stroke induction with the non-selective CB1/CB2 agonist WIN-55212, receptor antagonists, the selective CB2 agonist HU-308, or vehicle. Neurological deficits, infarct volume, cerebral inflammatory gene expression, and intestinal leukocyte-endothelial interactions following lipopolysaccharide (LPS) challenge were assessed using Neuroscore, TTC staining, RT-qPCR, and intravital microscopy. SIM-A9 microglia were used to evaluate the effects of HU-308 on viability and cytokine release under inflammatory conditions. PTS induced a CIDS-like phenotype characterized by reduced baseline leukocyte rolling and a markedly blunted leukocyte adhesion response following LPS challenge. Non-selective cannabinoid receptor activation improved neurological scores and reduced infarct size, while CB2 blockade abolished this protection. Selective CB2 activation with HU-308 reduced infarct volume, improved neurological outcome, and suppressed stroke-associated TNF and IL-6 expression in the ischemic hemisphere. In vitro, HU-308 reduced TNF release from LPS-stimulated microglia, while IL-4 enhanced microglial viability and IL-10 production. Importantly, HU-308 preserved leukocyte adhesion after LPS challenge following stroke, suggesting maintained peripheral immune responsiveness. These findings identify CB2 receptor activation as a promising neuroimmune strategy that limits acute stroke injury while attenuating the development of CIDS.

Infrasound, physically defined as sound at frequencies below 20 Hertz, can travel long distances with minimal attenuation and permeate biological tissues due to its marked particle displacement and deep penetration. Generated by both natural phenomena and human-made systems, infrasound has drawn increasing scientific and public attention regarding its potential physiological and psychological effects. Experimental studies demonstrate that infrasound can modulate mechanosensitive structures at the cellular level, particularly pressure-sensitive ion channels such as PIEZO1 and TRPV4, leading to intracellular calcium influx, oxidative stress, altered intercellular communication, and in some settings, apoptosis. These responses vary according to sound pressure levels, frequencies, exposure duration, and tissue type. In the cardiovascular system, higher sound pressures have been associated with mitochondrial injury and fibrosis, whereas low sound pressures may exert context-dependent protective effects. In animal models, prolonged or intense exposure to infrasound has been shown to induce neuroinflammatory responses and memory impairment. Short-term studies in humans at moderate intensities have reported minimal physiological changes, with psychological and contextual factors influencing symptom perception. Occupational environments such as factories and agricultural settings may contain elevated levels of infrasound, underscoring the importance of systematic measurements and exposure assessments. At the same time, controlled infrasound stimulation has shown potential as an adjunct modality in bone repair and tissue regeneration, highlighting its dual capacity as both a biological stressor and a possible therapeutic tool. Overall, existing data indicate that infrasound may be harmful at chronic exposure depending on intensity and frequency, yet beneficial when precisely regulated. Future research should standardize exposure metrics, refine measurement technologies, and clarify dose–response relationships to better define the health risks and therapeutic applications of infrasound.

Infrasound, physically defined as sound at frequencies below 20 Hertz, can travel long distances with minimal attenuation and permeate biological tissues due to its marked particle displacement and deep penetration. Generated by both natural phenomena and human-made systems, infrasound has drawn increasing scientific and public attention regarding its potential physiological and psychological effects. Experimental studies demonstrate that infrasound can modulate mechanosensitive structures at the cellular level, particularly pressure-sensitive ion channels such as PIEZO1 and TRPV4, leading to intracellular calcium influx, oxidative stress, altered intercellular communication, and in some settings, apoptosis. These responses vary according to sound pressure levels, frequencies, exposure duration and tissue type. In the cardiovascular system, higher sound pressures have been associated with mitochondrial injury and fibrosis, whereas low sound pressures may exert context-dependent protective effects. In animal models, prolonged or intense exposure to infrasound has been shown to induce neuroinflammatory responses and memory impairment. Short-term studies in humans at moderate intensities have reported minimal physiological changes, with psychological and contextual factors influencing symptom perception. Occupational environments such as factories and agricultural settings may contain elevated levels of infrasound, underscoring the importance of systematic measurements and exposure assessments. At the same time, controlled infrasound stimulation has shown potential as an adjunct modality in bone repair and tissue regeneration, highlighting its dual capacity as both a biological stressor and a possible therapeutic tool. Overall, existing data indicate that infrasound may be harmful at chronic exposure depending on intensity and frequency, yet beneficial when precisely regulated. Future research should standardize exposure metrics, refine measurement technologies, and clarify dose–response relationships to better define the health risks and therapeutic applications of infrasound.

Sepsis causes profound microcirculatory dysfunction, where heterogeneous capillary perfusion and abnormal vasomotion contribute to tissue hypoxia and organ failure. Sublingual videomicroscopy is established in large animals and humans to monitor these alterations, but this approach has not been applied in murine models. We developed a method to assess sublingual perfusion and vasomotion in mice using sidestream dark field (SDF) videomicroscopy. Male C57BL/6 mice were anesthetized, and sublingual vessels were imaged for 90 min. Perfusion and vasomotion parameters were assessed, and a Fast Fourier Transform was performed on vasomotion data to characterize the frequency components of rhythmic microvessel diameter changes. Another group of animals was administered lipopolysaccharide (LPS) intraperitoneally as a model of systemic inflammation in sepsis. LPS-treated mice exhibited a significant decline in the proportion of perfused vessels at 90 min and in the microvascular flow index. Very low-frequency vasomotion (0.005–0.15 Hz) declined in controls but was preserved during endotoxemia, suggesting an active microvascular tone response to inflammatory stress. This study establishes the first murine protocol for sublingual SDF imaging, allowing early detection of perfusion deficits and vasomotor changes in experimental sepsis. The minimal-invasive approach offers a translational platform for mechanistic and therapeutic studies in sepsis.

Sepsis causes profound microcirculatory dysfunction, where heterogeneous capillary perfusion and abnormal vasomotion contribute to tissue hypoxia and organ failure. Sublingual videomicroscopy is established in large animals and humans to monitor these alterations, but this approach has not been applied in murine models. We developed a method to assess sublingual perfusion and vasomotion in mice using sidestream dark field (SDF) videomicroscopy. Male C57BL/6 mice were anesthetized, and sublingual vessels were imaged for 90 minutes. Perfusion and vasomotion parameters were assessed, and a Fast Fourier Transform was performed on vasomotion data to characterize the frequency components of rhythmic microvessel diameter changes. Another group of animals was administered lipopolysaccharide (LPS) intraperitoneally as a model of systemic inflammation in sepsis. LPS-treated mice exhibited a significant decline in the proportion of perfused vessels at 90 minutes and in the microvascular flow index. Very low-frequency vasomotion (0.005–0.15 Hz) declined in controls but was preserved during endotoxemia, suggesting an active microvascular tone response to inflammatory stress. This study establishes the first murine protocol for sublingual SDF imaging, allowing early detection of perfusion deficits and vasomotor changes in experimental sepsis. The minimal-invasive approach offers a translational platform for mechanistic and therapeutic studies in sepsis.

Propofol is well-known for its inhibitory effects in the central nervous system (CNS) as an intravenous anesthetic. Less is known about propofol's impact on microglial activity. Studies have suggested a link to the endocannabinoid system (ECS). Propofol has been shown to indirectly modulate cannabinoid type 1 (CB1R) and type 2 (CB2R) receptors on microglia, with CB2R playing a key role in regulating anti-inflammatory immune responses. The objective of this study was to evaluate potential anti-inflammatory effects of propofol on microglia and to determine whether any observed effects are associated with the ECS. To investigate this, we treated LPS-stimulated SIMA9 microglial cells with propofol, both in the presence and absence of antagonists for CB2R and CB1R, and assessed the cell viability and the production of the cytokines TNF and IL-6. The results demonstrated that cell viability was stable at propofol concentrations of 20, 40, and 80 µM. Production of TNF and IL-6 was reduced significantly upon propofol treatment. This effect of cytokine production did not change following administration of CB1R and/or CB2R antagonists. In conclusion, the results demonstrated that propofol exhibits anti-inflammatory effects, which do not appear to be mediated through ECS activation.

Ischemic stroke, responsible for the majority of stroke cases worldwide, triggers profound neuroinflammatory responses largely mediated by microglia. Excessive activation of pro-inflammatory microglia exacerbates neuronal injury, highlighting the need for therapeutic strategies targeting microglial modulation. Propofol (2,6-diisopropylphenol), a widely used intravenous anesthetic, has emerged as a promising neuroprotective agent due to its potent anti-inflammatory properties. This review comprehensively explores the diverse cellular mechanisms by which propofol attenuates microglial activation and inflammation in ischemic stroke. By elucidating these molecular pathways, it underscores the therapeutic potential of propofol in mitigating ischemic brain injury and guiding future clinical interventions.

Iron is a key nutritional requirement for a variety of physiological functions, and its metabolism is tightly controlled under homeostatic conditions. The endocannabinoid system (ECS) represents an additional physiological system with a key role in maintaining homeostasis that is known for its role in modulating immune responses. Recent research has highlighted intriguing interactions between these systems, including the suppression of iron uptake by the ECS and alterations to the iron-catalyzed Fenton reaction. These interactions are particularly interesting in the context of bacterial infections. As iron is a vital nutrient for bacteria, modulating iron levels using the ECS may be able to control bacterial growth. This review aims to explore the current understanding of how the ECS affects iron homeostasis and its implications for bacterial pathogenesis. In this study, we provide an overview of both iron metabolism and the ECS, focusing on harnessing these systems to develop novel therapeutic strategies to modulate iron metabolism in bacterial infections. By elucidating these complex interactions, we hope to provide new insights into the development of novel treatments for bacterial infections.