Embryonic Pericytes Promote Microglial Homeostasis and Their Effects on Neural Progenitors in the Developing Cerebral Cortex.

Multifaceted microglial functions in the developing brain, such as promoting the differentiation of neural progenitors and contributing to the positioning and survival of neurons, have been progressively revealed. Although previous studies have noted the relationship between vascular endothelial cells and microglia in the developing brain, little attention has been given to the importance of pericytes, the mural cells surrounding endothelial cells. In this study, we attempted to dissect the role of pericytes in microglial distribution and function in developing mouse brains. Our immunohistochemical analysis showed that approximately half of the microglia attached to capillaries in the cerebral walls. Notably, a magnified observation of the position of microglia, vascular endothelial cells and pericytes demonstrated that microglia were preferentially associated with pericytes that covered 79.8% of the total capillary surface area. Through in vivo pericyte depletion induced by the intraventricular administration of a neutralizing antibody against platelet-derived growth factor receptor (PDGFR)ß (clone APB5), we found that microglial density was markedly decreased compared with that in control antibody-treated brains because of their low proliferative capacity. Moreover, in vitro coculture of isolated CD11b+ microglia and NG2+PDGFRα- cells, which are mostly composed of pericytes, from parenchymal cells indicated that pericytes promote microglial proliferation via the production of soluble factors. Furthermore, pericyte depletion by APB5 treatment resulted in a failure of microglia to promote the differentiation of neural stem cells into intermediate progenitors. Taken together, our findings suggest that pericytes facilitate microglial homeostasis in the developing brains, thereby indirectly supporting microglial effects on neural progenitors.SIGNIFICANCE STATEMENT This study highlights the novel effect of pericytes on microglia in the developing mouse brain. Through multiple analyses using an in vivo pericyte depletion mouse model and an in vitro coculture study of isolated pericytes and microglia from parenchymal cells, we demonstrated that pericytes contribute to microglial proliferation and support microglia in efficiently promoting the differentiation of neural stem cells into intermediate progenitors. Our present data provide evidence that pericytes function not only in the maintenance of cerebral microcirculation and blood brain barrier (BBB) integrity but also in microglial homeostasis in the developing cerebral walls. These findings will expand our knowledge and help elucidate the mechanism of brain development both in healthy and disease conditions.

Effect of stabilization splint on occlusal force distribution during voluntary submaximal tooth clenching: a preliminary sleep simulation study.

The purpose of the study was to clarify the effect of a stabilization splint (SS) on the distribution of occlusal force around the dental arch during voluntary submaximal tooth clenching. Ten healthy volunteers participated in this study. For each subject, the maxillary SS was made of heat-cured hard acrylic resin with approximately one mm thickness at the molar regions. The subjects were asked to perform static clenching at either 40% or 80% maximum voluntary contraction (MVC) levels, with and without the SS in place, using visual feedback. The occlusal contact area and occlusal force were analyzed. When the SS was inserted, the mean tooth contact area and occlusal force significantly decreased at both 40% and 80% MVC levels (p < 0.01). The location of the occlusal balancing point changed towards the anterior after insertion of the SS. The results suggest that the SS has potential to reduce individual tooth-loading forces by evenly distributing the forces generated during sleep bruxism.

Efficient fabrication of ordered alumina through-hole membranes using a TiO2 protective layer prepared by atomic layer deposition.

Ordered alumina through-hole membranes were obtained by a combination of the anodization of Al, formation of a TiO2 protective layer, and subsequent etching. Two-layered anodic porous alumina materials composed of TiO2-coated and noncoated alumina were prepared by the combination of the anodization of Al and the formation of a TiO2 protective layer by atomic layer deposition (ALD). The obtained two layers of anodic porous alumina have different solubilities because the TiO2 thin layer formed by ALD acts as a protective layer that prevents the dissolution of the alumina layer during wet etching of the sample in an etchant. After the selective dissolution of the bottom layer of porous alumina without the TiO2 layer, an ordered alumina through-hole membrane could be detached from the Al substrate. This process allows the repeated preparation of ordered alumina through-hole membranes from a single Al substrate. By this process, ordered alumina through-hole membranes with large interhole distances could also be obtained. The obtained alumina through-hole membrane can be used in various applications.