Pericytes in Neurometabolic Diseases
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PERICYTES (A BIRBRAIR, SECTION EDITOR)
Pericytes in Neurometabolic Diseases Eugenia Isasi 1,2 & Silvia Olivera-Bravo 2
# Springer Nature Switzerland AG 2020
Abstract Purpose of Review Since brain pericytes guarantee appropriate development and maintenance of the cerebrovascular system, we reviewed their role in neurometabolic diseases (NMDs), a subclass of inborn errors of metabolism that selectively cause neurological sequels and widespread cerebrovascular alterations. Recent Findings Main findings about pericyte involvement in NMDs arise from glutaric acidemia type I (GA-I) models. In this regard, we found that (i) a single intracisternal injection of the main accumulated metabolite (glutaric acid, GA) in rat neonates disturbed the neurovascular unit (NVU) as evidenced by blood-brain barrier hyperpermeability, and altered immunoreactivity of pericyte and astrocyte markers surrounding brain microvessels; (ii) GA-elicited capillary constriction near pericyte somata likely inducing reduced brain blood flow as reported in GA-I patients; (iii) GA-elicited pericyte contraction probably results from a defective interplay among NVU components and could be relevant in case of metabolic decompensation or energetic deficiency. Summary Although pericyte pathological features have been studied in few NMDs, their involvement in NMD pathophysiology is largely unknown. Thus, further studies are needed to identify their roles and therapeutic potentiality. Keywords Neurometabolic diseases . Inborn errors of metabolism . Glutaric acidemia type I . Neurovascular unit . Pericytes . Metabolic stroke
Introduction An extensive analysis of the concept of inborn errors of metabolism (IEM) as well as that of neurometabolic diseases (NMDs) is necessary to understand the role of pericytes in the vascular alterations that are pathognomonic signs in most of NMDs and a great percentage of IEMs. The expression “inborn error of metabolism” was addressed in 1908 by Sir Archibald Garrod to describe a group of disorders that might result from metabolic failures. Garrod also noted that IEMs were present at birth, persisted throughout life, were This article is part of the Topical Collection on Pericytes * Silvia Olivera-Bravo [email protected] Eugenia Isasi [email protected] 1
Department of Histology and Embriology, Faculty of Medicine, University of the Republic, Gral. Flores Av., 2125, Montevideo, Uruguay
2
Cell and Molecular Neurobiology, Clemente Estable Institute (IIBCE), 3318 Italia Av., Montevideo, Uruguay
recessively inherited following Mendel’s laws, and did not respond to medical treatment [1]. Nowadays, the concept also includes a few genetic alterations that are not inheritably transmitted and involves around 600 different rare diseases of complex pathophysiology, diagnosis, and therapeutic options, all of them with a collective incidence greater than 1:1000 living births [2, 3]. Moreover, if the concept is extended and includes the impairment of specific enzymes or biochemical pathways that are intrinsic to the pathome
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