Cell . . . Create a visual network map of the cerebrovascular vessels.

There is a complex and dense network of arteries, capillaries and veins in the brain.the characteristics of high metabolic demand and low energy storage capacity of the brain require that the maintenance of neuronal function is closely related to the normal operation of vascular system.slight disturbance of blood flow will affect the function of neurons and lead to neuron damage.the activity of neurons can also regulate the blood circulation of the brain.many nervous system diseases involve vascular components, and most of the changes in blood vessels will also affect brain function [1].it is very challenging to study the changes of cerebral blood vessels and vascular tissues in diseases.the cerebral vascular system spans multiple scales, ranging from microns of capillaries to a few millimeters of blood vessels, forming a highly complex network.and the blood exchange of the brain is strictly controlled by the blood-brain barrier.the combination of two-photon microscopy and brain micro window technology has become a necessary condition for the study of blood flow and metabolic dynamics in vivo.because it is difficult to master the whole cerebral vascular tissue information, the influence of vascular topological heterogeneity on the function of neural circuit is usually not well reflected.to solve these problems, we need to analyze the fine structure of cerebral vascular network.the method of recognizing arteries, capillaries and veins is fully revealed for the tissue structure of vascular system.at present, large-scale cerebrovascular reconstruction is mainly carried out by filling method, combining optical materials and optical microscope.despite the use of improved vascular filling materials to clearly label vessels for imaging and downstream analysis, and improved injection methods, the nature of the reconstructed vessels remains unclear.transgenic mice were used to label mouse vessels, but the labeling was fuzzy and discontinuous, and the vascular center was not labeled, which led to the failure to provide high-resolution images and the lack of requirements for large-scale image processing [2].recently, Nicolas Renier, from Sorbonne University in Paris, France, published an article on cell entitled mapping the fine scale organization and plasticity of the brain vacuum.this study developed a tissue-based immunolabeling technique to image the cerebral vascular network of adult mice, and segmented the TB level multi-channel images through the optical microscope with a special tube (tubemap), so as to construct a visual vascular map composed of more than 100 million vascular segments for subsequent analysis.in this paper, the author first used idisco + method to treat mouse brain, which did not affect the integrity of cerebral vascular system.due to the change of epitope density, it is very challenging to label the endothelial cells completely with antibodies.in order to enhance the signal-to-noise ratio of immunolabeling, the authors used a mixture of "super polyclonal" (a series of antibodies against proteins widely expressed in endothelial cells), including CD31, collagen IV and podocalyxin.the arteries were labeled with ACTA2 and Transgelin (SM22), and veins were labeled with ACTA2 and vWF.the author has developed a wobbly sticher system for imaging, which can eliminate the limitation of data imaging duplication and generate continuous vascular images.and the filter set arranged by multi-path is used to process complex fluorescent images quickly.the authors used the brains of more than 20 adult mice to generate data sets of labeled arteries, veins and vessels.according to its anatomical region, the vascular network including capillaries in the whole brain region was characterized.vascular network imaging reveals the correlation between the distribution characteristics of local vascular network and local brain function, and puts forward the classification strategy of cortical region based on the topological characteristics of blood vessels.mapping the cerebral vascular system also confirmed the high heterogeneity of capillary density in the whole brain.the change of capillary density was not related to the density of neurons, but to the level of oxidative metabolism of synapses.high capillary density is located in the synaptic terminal region with high ATP abundance, such as in the sensory nerve circuit, where the level of oxidative metabolism is high.the cerebral vascular network is a highly plastic system.when various types of brain injury occur, large-scale rearrangement of vascular network occurs.during embryonic development and early postnatal development, neuronal activity can also lead to vascular network remodeling.the authors then analyzed the whole brain rearrangement of vascular topology in animal models of congenital deafness and ischemic stroke. in the induced cerebral ischemia model, directional remodeling based on vascular density maintenance is an important factor of vascular plasticity in adult mice. in OTOF - / - mice with congenital deafness, we found that the brain can compensate for the loss of auditory input across regions. the vascular density of some integration areas, such as the peripheral and marginal areas closely connected with the sensory cortex, increased in deaf mice, indicating the plasticity and adaptability of vascular network development. this research has developed a new method of cerebral vascular imaging to help explore the correlation between cerebral vascular network and function. in the future, it will help to reveal the relationship between neuronal dysfunction and metabolism. at present, studies have suggested that there is a close relationship between cerebrovascular system and cognitive disorders, such as autism and schizophrenia. however, the technical requirements and time cost of evaluating the relationship between vascular system and neuron function are still daunting. The new method developed in this paper provides a feasible research tool. original link: platemaker: Ke, reference: 1. Kisler, K., Nelson, A.R., Montagne, A., and zlokovic, B.V. (2017). Cerebral blood flow regulation and neurovascular dysfunction in Alzheimer disease. NAT. Rev. Neurosci. 18, 419 – 434.2. Jing, D., Zhang, S., Luo, W., Gao, Gao, X., men, y, Ma, C., Liu, X., Yi, Yi, Yi, Yi, Yi, Yi, Yi, Yi, Yi, Yi, Yi, Yi, Yi, Yi, Yi, Yi, Yi, Yi, Yi, Yi, Yi, Yi, Yi, Yi, Yi, Li, Li, Li, Li, Li, Li, Li, Li, Li, Li,, Y., bugde, A., Zhou, B.O., et al al. (2018). Tissue clearing of both hard and soft tissue organs with the PEGASOS method. Cell Res. 28, 803–818.