Perivascular macrophages in cerebrovascular diseases.

Cerebrovascular diseases are a major cause of stroke and dementia, both requiring long-term care. These diseases involve multiple pathophysiologies, with mitochondrial dysfunction being a crucial contributor to the initiation of inflammation, apoptosis, and oxidative stress, resulting in injuries to neurovascular units that include neuronal cell death, endothelial cell death, glial activation, and blood-brain barrier disruption. To maintain brain homeostasis against these pathogenic conditions, brain immune cells, including border-associated macrophages and microglia, play significant roles as brain innate immunity cells in the pathophysiology of cerebrovascular injury. Although microglia have long been recognized as significant contributors to neuroinflammation, attention has recently shifted to border-associated macrophages, such as perivascular macrophages (PVMs), which have been studied based on their crucial roles in the brain. These cells are strategically positioned around the walls of brain vessels, where they mainly perform critical functions, such as perivascular drainage, cerebrovascular flexibility, phagocytic activity, antigen presentation, activation of inflammatory responses, and preservation of blood-brain barrier integrity. Although PVMs act as scavenger and surveillant cells under normal conditions, these cells exert harmful effects under pathological conditions. PVMs detect mitochondrial dysfunction in injured cells and implement pathological changes to regulate brain homeostasis. Therefore, PVMs are promising as they play a significant role in mitochondrial dysfunction and, in turn, disrupt the homeostatic condition. Herein, we summarize the significant roles of PVMs in cerebrovascular diseases, especially ischemic and hemorrhagic stroke and dementia, mainly in correlation with inflammation. A better understanding of the biology and pathobiology of PVMs may lead to new insights on and therapeutic strategies for cerebrovascular diseases.

Low-fat yogurt consumption maintains biomarkers of immune function relative to nondairy control food in women with elevated BMI: A randomized controlled crossover trial.

Yogurt consumption may help reduce chronic inflammation associated with obesity. However, the underlying mechanism(s) by which yogurt consumption modulates the immune system have not been validated in human intervention studies. We hypothesized that 4-week yogurt consumption (12 oz/day) attenuates systemic inflammation by modulating the proportion of circulating T helper (Th) 17 and regulatory T (Treg) cells in adult women with elevated body mass index (BMI). To test the hypothesis, we conducted a randomized crossover dietary intervention study consisted of a 4-week dietary intervention in which participants consumed 12 oz of either low-fat dairy yogurt or a soy pudding control snack per day, with a 4-week washout between treatments. Thirty-nine healthy adult women with a BMI between 25 and 40 kg/m2 were enrolled and 20 completed the study. Changes in the biometrics, circulating T cells, and markers of systemic and colonic inflammation were assessed between the 2 treatment groups, as well as 24-hour diet recalls were conducted at baseline and following each treatment. The primary study outcome, the change in the proportion of circulating Th17 cells, was unaffected by the treatments. Secondary outcome measures, circulating Treg, Th17, and markers of chronic inflammation, were maintained by yogurt treatment, whereas circulating Treg was increased and interleukin-10 was reduced by control snack treatment. However, circulating Treg changes were not associated with changes to other biomarkers of inflammation, implying other immune cells and/or tissues may mediate circulating biomarkers of chronic inflammation. This study was approved by the University of Wisconsin-Madison institutional review board and registered at ClinicalTrials.gov NCT04149418.