Brain microvascular pericytes in health and disease |
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Authors: | Dalkara Turgay Gursoy-Ozdemir Yasemin Yemisci Muge |
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Institution: | (1) Department of Neurology, Faculty of Medicine and, Institute of Neurological Sciences and Psychiatry, Hacettepe University, Sihhiye, Ankara, Turkey |
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Abstract: | Pericytes are located at periphery of the microvessel wall and wrap it with their processes. They communicate with other cells
of the neurovascular unit by direct contact or through signaling pathways and regulate several important microcirculatory
functions. These include development and maintenance of the blood–brain barrier (BBB), distribution of the capillary blood
flow to match the local metabolic need of the nearby cells, and angiogenesis. Pericytes also exhibit phagocytic activity and
may function as pluripotent stem cells. Increasing evidence suggests a role for pericytes in a wide range of CNS diseases.
They appear to be vulnerable to oxygen and nitrogen radical toxicity and have been shown to contract during cerebral ischemia
and remain contracted despite reopening of the occluded artery. This causes impaired re-flow and may diminish the benefit
of re-canalization therapies in stroke patients. Hyperglycemia-induced dysfunction of the signaling pathways between pericytes
and endothelia is thought to play an important role in diabetic retinopathy, a common cause of blindness. Amyloid deposits
detected within degenerating pericytes in the brains of patients with Alzheimer’s disease suggest that pericyte dysfunction
may play a role in cerebral hypoperfusion and impaired amyloid β-peptide clearance in Alzheimer’s disease. This exciting possibility
may reveal a novel temporal sequence of events in chronic neurodegeneration, in which microvascular dysfunction due to pericyte
degeneration initiates secondary neurodegenerative changes. Identification of molecular mechanisms by which pericytes regulate
BBB integrity in inflammatory conditions as well as in vasogenic brain edema may lead to new treatments. Pericytes may also
take part in tissue repair and vascularization after CNS injury. In conclusion, although the evidence is just emerging and
mostly preliminary, disclosing pericytes’ role in the pathophysiology of CNS diseases may yield exciting developments and
novel treatments. |
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