Open AccessProtection of the neurovascular unit from calcium-related ischemic injury by linalyl acetate
Author(s) -
Yu Shan Hsieh,
You Kyoung Shin,
Geun Hee Seol
Publication year - 2021
Publication title -
chinese journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.396
H-Index - 31
eISSN - 2666-0059
pISSN - 0304-4920
DOI - 10.4103/cjp.cjp_94_20
Subject(s) - chemistry , reactive oxygen species , lactate dehydrogenase , nitric oxide , microglia , nadph oxidase , pharmacology , context (archaeology) , cell damage , microbiology and biotechnology , biochemistry , inflammation , immunology , biology , enzyme , paleontology , organic chemistry
Calcium-related ischemic injury (CRII) can damage cells of the neurovascular unit (NVU). Here, we investigate the protective effects of linalyl acetate (LA) against CRII-induced NVU damage and evaluate the underlying mechanisms. The protective effects of LA in cell lines representative of NVU components (BEND, SH-SY5Y, BV2, and U373 cells) were evaluated following exposure to oxygen-glucose deprivation/reoxygenation alone (OGD/R-only) or OGD/R in the presence of 5 mM extracellular calcium ([Ca 2+ ] o ) to mimic CRII. LA reversed damage under OGD/R-only conditions by blocking p47 phox /NADPH oxidase (NOX) 2 expression, reactive oxygen species (ROS) production, nitric oxide (NO) abnormality, and lactate dehydrogenase (LDH) release only in the BEND cells. However, under CRII-mimicking conditions, LA reversed NO abnormality and matrix metalloproteinase (MMP)-9 activation in the BEND murine brain endothelial cells; inhibited p47 phox expression in the human SH-SY5Y neural-like cells; decreased NOX2 expression and ROS generation in the BV2 murine microglial cells; and reduced p47 phox expression in the U373 human astrocyte-like cells. Importantly, LA protected against impairment of the neural cells, astrocytes, and microglia, all of which are cellular components of the NVU induced by exposure to CRII-mimicking conditions, by reducing LDH release. We found that LA exerted a protective effect in the BEND cells that may differ from its protective effects in other NVU cell types, following OGD/R-induced damage in the context of elevated [Ca 2+ ] o .