Circadian rhythms regulate the time of day at which various physiological processes take place, including the functions of the kidney. This regulation is made possible by key transcriptional regulators: the core molecular circadian clock, which mediates expression of clock-controlled genes on a 24-h cycle. The present landscape of circadian rhythm research in the kidney spans impacts on the clinical level as well as in basic research, where its role in individual kidney cell types, disease states, and the impacts of environmental stressors is being studied. Recent research has also identified sex differences, cross talk between various tissues, and immune signaling as important considerations for understanding the circadian clocks within the kidney. This review synthesizes the current knowledge of circadian rhythms of the kidney in regard to these issues and stresses the importance of time of day in research as well as in patient health.
Probiotics are widely used live microbial supplements intended to promote human health, yet their clinical benefits remain inconsistent and often strain-specific. Most currently available probiotics are derived from Lactobacillus , Bifidobacterium , and Saccharomyces species originally isolated from fermented foods or human microbiota. Preclinical studies suggest that these organisms may influence host physiology through several mechanisms, including antimicrobial activity, toxin inhibition, strengthening of intestinal barrier function, modulation of immune responses, and signaling along the gut–brain axis. However, translation of these mechanisms into consistent clinical benefit has been limited by heterogeneity in probiotic strains, dosing, and study design. Emerging evidence also highlights potential unintended consequences of probiotic use, including rare infections in vulnerable patients, alterations of microbiome recovery after antibiotics, and possible interactions with host metabolism or medications. Recent advances in microbiome research have supported the development of next-generation probiotics and engineered microbial therapeutics, representing a shift toward more targeted and mechanistically informed live microbial therapies.
Flow disturbances in the smallest blood vessels of the brain, the capillaries, have long been considered a potential cause of brain dysfunction. However, owing to the technological challenge of studying blood flow in three-dimensional capillary networks, elucidating the incidence, causes, and consequences of capillary obstructions has been difficult. Advances in optical microscopes for in vivo imaging, primarily high-spatiotemporal-resolution optical coherence tomography and two-photon microscopy, have recently enabled detailed studies of these capillary stalling events in both healthy and diseased mice. In this review, we describe these imaging approaches to quantify capillary stalling, identifying strengths and weaknesses of different methods. We then review recent findings on the incidence, molecular and cellular causes, and physiological and neurological consequences of capillary stalling across multiple mouse models of brain disease, including Alzheimer's disease, stroke, and traumatic brain injury. We conclude by suggesting necessary next steps in instrumentation and analysis for studying capillary stalling, as well as how to address key unanswered questions about underlying mechanisms for capillary stalling in the brain and how this phenomenon may impact disease progression and cognitive function.
The myogenic tone and thus diameter of brain arterioles varies on multiple time scales. These variations result from coordinated contraction and relaxation of electrically coupled smooth muscle cells in the arteriole wall that drive constriction. A prominent feature is a broad-band ∼0.1 Hz rhythmicity, designated vasomotion, in the pial arterioles spanning the cortical mantle and the penetrating arterioles that nourish the capillary bed. As characterized in the murine brain, vasomotion supports propagating waves with a typical wavelength of 20 mm (a speed of 2 mm/s) that modulate perfusion with a magnitude equal to that of functional hyperemia. The spectral and spatial properties reflect the interaction of smooth muscle dynamics with the underlying neuronal drive. Possible functional roles of vasomotion are to mitigate capillary stalls and to facilitate the exchange of solutes between interstitial and cerebrospinal fluid. Indeed, loss of vasomotion has been implicated in the pathophysiology of vascular disease, such as cerebral amyloid angiopathy.
