著者

髙橋 愼一

出版者

日本神経治療学会

雑誌

神経治療学 (ISSN:09168443)

巻号頁・発行日

vol.35, no.3, pp.163-166, 2018 (Released:2018-12-25)

参考文献数

26

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The neurovascular unit (NVU) is a conceptual framework used to better understand the normal physiological interaction between neurons and microvessels as well as the pathophysiology of cerebral ischemia. The major components of the NVU consist of neurons, microvessels, and astrocytes that are interposed between the neuronal synapse and the microvasculature. In addition, other types of glial cells (microglia and oligodendroglia), pericytes, and the extracellular matrix (ECM) play important roles in the neurovascular coupling that enables microvessels to supply adequate glucose and oxygen to neurons when activated. The close proximity of microvessels to astroglial end–feet and the metabolic support of astrocytes for neurons suggest that communication could also be directed from microvessels to the neurons. Regarding alternative energy substrates other than glucose, the highly active astroglial glycolytic pathway provides neurons with lactate as a TCA cycle substrate. In addition, ketone bodies are thought to be generated mainly in astroglia to fuel neurons. The shunt pathway of glycolysis, the pentose–phosphate pathway, plays a pivotal role in the maintenance of NADPH, which that is necessary to protect both neurons and microvessels against reactive oxygen species (ROS). In fact, ROS induces neuronal pyruvate dehydrogenase complex (PDHC) dysfunction and ECM degradation, leading to hemorrhagic transformation after reperfusion. Astrocyte–derived ketone bodies can be utilized by the neuronal TCA cycle even after ischemic insult, since PDHC is not required for their metabolism. The concept of the NVU has expanded our understanding of pathophysiology and aided the development of novel therapeutic strategies against neurodegenerative diseases, neuro–immunological disorders, and stroke.