ST2, amemberoftheinterleukin(IL)1receptorfamily,anditsligandIL-33playcriticalrolesinimmuneregulationandinflammatoryresponses. This study explores the roles of endogenous IL-33/ST2 signaling in ischemic brain injury and elucidates the underlying mechanisms of action. The expression of IL-33 rapidly increased in oligodendrocytes and astrocytes after 60 min transient middle cerebral artery occlusion (tMCAO). ST2 receptor deficiency exacerbated brain infarction 3 d after tMCAO as well as distal permanent MCAO. ST2 deficiency also aggravated neurologicaldeficitsupto7daftertMCAO.Conversely,intracerebroventricularinfusionsofIL-33aftertMCAOattenuatedbraininfarction.Flow cytometry analyses demonstrated high levels of ST2 expression on microglia, and this expression was dramatically enhanced after tMCAO. The absence of ST2 enhanced the expression of M1 polarization markers on microglia/macrophages, and impaired the expression of M2 polarization markers after tMCAO. In vitro studies on various types of cultures and coculture systems confirmed that IL-33/ST2 signaling potentiated expression of IL-10 and other M2 genes in primary microglia. The activation of ST2 on microglia led to a protective phenotype that enhanced neuronal survival against oxygen glucose deprivation. Further in vitro studies revealed that IL-33-activated microglia released IL-10, and that this was critical for their neuroprotective effects. Similarly, intracerebroventricular infusions of IL-33 into IL-10 knockout mice failed to provide neuroprotection against tMCAO in vivo. These results shed new light on the IL-33/ST2 axis as an immune regulatory mechanism that serves as a natural brake on the progression of ischemic brain injury.

White matter (WM) occupies a large volume of the human cerebrum and is mainly composed of myelinated axons and myelin-producing glial cells. The myelinated axons within WM are the structural foundation for efficient neurotransmission between cortical and subcortical areas. Similar to neuron-enriched gray matter areas, WM undergoes a series of changes during the process of aging. WM malfunction can induce serious neurobehavioral and cognitive impairments. Thus, age-related changes in WM may contribute to the functional decline observed in the elderly. In addition, aged WM becomes more susceptible to neurological disorders, such as stroke, traumatic brain injury (TBI), and neurodegeneration. In this review, we summarize the structural and functional alterations of WM in natural aging and speculate on the underlying mechanisms. We also discuss how age-related WM changes influence the progression of various brain disorders, including ischemic and hemorrhagic stroke, TBI, Alzheimer’s disease, and Parkinson’s disease. Although the physiology of WM is still poorly understood relative to gray matter, WM is a rational therapeutic target for a number of neurological and psychiatric conditions.

BackgroundTraumatic brain injury (TBI) is one of the major causes of mortality and disability for all ages worldwide. Mesenchymal stem cells (MSCs)-originated exosomes have provided therapeutic effects. However, as an indispensable component of MSCs, whether odontogenic stem cell-generated exosomes could benefit TBI is still unclear. Thus we aimed to explore the potential of stem cells from human exfoliated deciduous teeth-originated exosomes (SHED-Ex) for the management of TBI.MethodsFirst, a transwell system was used to co-culture activated BV-2 microglia cells with SHED. The secretion levels of neuroinflammatory factors and nitrite were evaluated by enzyme-linked immunosorbent assay (ELISA) and Griess assay. Furthermore, purified SHED-Ex were co-cultured with activated BV-2. ELISA, Griess assay, flow cytometry, immunofluorescence, and qRT-PCR were performed to test the levels of inflammatory factors as well as the microglia phenotype. Finally, SHED and SHED-Ex were locally injected into TBI rat models. Basso, Beattie, and Bresnahan (BBB) scores were chosen to evaluate the motor functional recovery. Histopathology and immunofluorescence were performed to measure the lesion volume and neuroinflammation.ResultsAs a result, SHED-Ex could reduce neuroinflammation by shifting microglia polarization. The administration of SHED-Ex improves rat motor functional recovery and reduces cortical lesion compared with the control group 2 weeks post-injury (P < 0.05).ConclusionsThe current study demonstrates for the first time that SHED-Ex contribute a therapeutic benefit to TBI in rats, at least in part by shifting microglia polarization to reduce neuroinflammation. The use of odontogenic stem cells, and indeed their exosomes, may be expanded for the treatment of TBI or other neurological disorders.

Roseburia intestinalis is an anaerobic, Gram-positive, slightly curved rod-shaped flagellated bacterium that produces butyrate in the colon. R. intestinalis has been shown to prevent intestinal inflammation and maintain energy homeostasis by producing metabolites. Evidence shows that this bacterium contributes to various diseases, such as inflammatory bowel disease, type 2 diabetes mellitus, antiphospholipid syndrome, and atherosclerosis. This review reveals the potential therapeutic role of R. intestinalis in human diseases. Patients with inflammatory bowel disease exhibit significant changes in R. intestinalis abundance, and they may benefit a lot from modulations targeting R. intestinalis. The data reviewed here demonstrate that R. intestinalis plays its role in regulating barrier homeostasis, immune cells, and cytokine release through its metabolite butyrate, flagellin and other. Recent advancements in the application of primary culture technology, culture omics, single-cell sequencing, and metabonomics technology have improved research on Roseburia and revealed the benefits of this bacterium in human health and disease treatment.