Nanotubular structures, denoted tunneling nanotubes (TNTs) have been described in recent times as involved in cell-to-cell communication between distant cells. Nevertheless, TNT-like, long filopodial processes had already been described in the last century as connecting facing, growing microvessels during the process of cerebral cortex vascularization and collateralization. Here we have investigated the possible presence and the cellular origin of TNTs during normal brain vascularization and also in highly vascularized brain tumors.We searched for TNTs by high-resolution immunofluorescence confocal microscopy, applied to the analysis of 20-µm, thick sections from lightly fixed, unembedded samples of both developing cerebral cortex and human glioblastoma (GB), immunolabeled for endothelial, pericyte, and astrocyte markers, and vessel basal lamina molecules.The results revealed the existence of pericyte-derived TNTs, labeled by proteoglycan NG2/CSPG4 and CD146. In agreement with the described heterogeneity of these nanostructures, ultra-long (> 300 µm) and very thin (< 0.8 µm) TNTs were observed to bridge the gap between the wall of distant vessels, or were detected as short (< 300 µm) bridging cables connecting a vessel sprout with its facing vessel or two apposed vessel sprouts. The pericyte origin of TNTs ex vivo in fetal cortex and GB was confirmed by in vitro analysis of brain pericytes, which were able to form and remained connected by typical TNT structures.None of the multiple roles described for TNTs can be excluded from a possible involvement during the processes of both normal and pathological vessel growth. A possible function, suggested by the pioneering studies made during cerebral cortex vascularization, is in cell searching and cell-to-cell recognition during the processes of vessel collateralization and vascular network formation. According to our results, it is definitely the pericyte-derived TNTs that seem to actively explore the surrounding microenvironment, searching for (site-to-site recognition), and connecting with (pericyte-to-pericyte and/or pericyte-to-endothelial cell communication), the targeted vessels. This idea implies that TNTs may have a primary role in the very early phases of both physiological and tumor angiogenesis in the brain.

Mariella Errede

Domenica Mangieri

Giovanna Longo

Francesco Girolamo

Ignazio de Trizio

Antonella Vimercati

Gabriella Serio

Karl Frei

Roberto Perris

Daniela Virgintino

Fluids and Barriers of the CNS

FLUIDS AND BARRIERS OF THE CNS 是一本开放获取、同行评审的期刊，考虑所有 CNS 液体和屏障系统在健康和疾病中的手稿。通过脑液和屏障的正常功能维持神经系统内部环境的稳态至关重要为了机体的健康。脑脊液 (CSF) 及其组成、循环和吸收在正常和异常的脑功能中具有多种作用，并且与脑实质间质液和血脑屏障处的神经血管单元密切相关。包括血脑脊液屏障、血脑屏障、血视网膜屏障和血神经屏障在内的中枢神经系统流体和屏障系统执行流体分泌、化学信号传导、物理和化学缓冲、专门的定向运输和促进免疫监视。

Fluids and Barriers of the CNS is an open-access, peer-reviewed journal that focuses on the study of central nervous system (CNS) fluids and barrier systems in health and disease. Cerebrospinal fluid (CSF) and its components, circulation, and absorption play critical roles in normal and abnormal brain function, closely interacting with the neurovascular unit at the brain parenchyma interstitial fluid and the blood-brain barrier. The fluid and barrier systems of the central nervous system, including the blood-cerebrospinal fluid barrier, blood-brain barrier, blood-retinal barrier, and blood-nerve barrier, are responsible for fluid secretion, chemical signaling, physical and chemical buffering, specialized directional transport, and facilitating immune surveillance, all of which are essential for maintaining the homeostasis of the internal environment of the nervous system.

《Fluids and Barriers of the CNS》是一本开放获取、同行评审的期刊，专注于中枢神经系统（CNS）液体和屏障系统在健康与疾病中的研究。脑脊液（CSF）及其成分、循环和吸收在正常和异常脑功能中发挥着重要作用，并与脑实质间质液和血脑屏障的神经血管单元密切相关。中枢神经系统的液体和屏障系统，包括血脑脊液屏障、血脑屏障、血视网膜屏障和血神经屏障，负责流体分泌、化学信号传导、物理和化学缓冲、特定的定向运输以及促进免疫监视，这些功能对于维持神经系统内部环境的稳态至关重要。

Tunneling nanotubes evoke pericyte/endothelial communication during normal and tumoral angiogenesis

The pericyte origin of TNTs ex vivo in fetal cortex and GB was confirmed by in vitro analysis of brain pericytes, which were able to form and remained connected by typical TNT structures, implying that TNTs may have a primary role in the very early phases of both physiological and tumor angiogenesis in the brain.

Category	Quartile
医学	1
医学, 神经科学	2

Tunneling nanotubes evoke pericyte/endothelial communication during normal and tumoral angiogenesis

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