title: Differential expression of the calcium-sensing receptor in the ischemic and border zones after transient focal cerebral ischemia in rats.
abstract: G-protein-coupled calcium-sensing receptor (CaSR) has been recently recognized as an important modulator of diverse cellular functions, beyond the regulation of systemic calcium homeostasis. To identify whether CaSR is involved in the pathophysiology of stroke, we studied the spatiotemporal regulation of CaSR protein expression in rats undergoing transient focal cerebral ischemia, which was induced by middle cerebral artery occlusion. We observed very weak or negligible immunoreactivity for CaSR in the striatum of sham-operated rats, as well as in the contralateral striatum of ischemic rats after reperfusion. However, CaSR expression was induced in the ischemic and border zones of the lesion in ischemic rats. Six hours post-reperfusion there was an upregulation of CaSR in the ischemic zone, which seemed to decrease after seven days. This upregulation preferentially affected some neurons and cells associated with blood vessels, particularly endothelial cells and pericytes. In contrast, CaSR expression in the peri-infarct region was prominent three days after reperfusion, and with the exception of some neurons, it was mostly located in reactive astrocytes, up to day 14 after ischemia. On the other hand, activated microglia/macrophages in both the ischemic and border zones were devoid of specific labeling for CaSR at any time point after reperfusion, despite their massive infiltration in both regions. Our results show heterogeneity in CaSR-positive cells within the ischemic and border zones, suggesting that CaSR expression is regulated in response to the altered extracellular ionic environment caused by ischemic injury. Thus, CaSR may have a multifunctional role in the pathophysiology of ischemic stroke, possibly in vascular remodeling and astrogliosis.
authors.affiliation: Department of Anatomy, Catholic Neuroscience Institute, Cell Death Disease Research Center, College of Medicine, The Catholic University of Korea, 137-701 Seoul, South Korea.
authors.forename: Jeong Sook
authors.initials: JS
authors.lastname: Noh
authors.affiliation: Department of Anatomy, Catholic Neuroscience Institute, Cell Death Disease Research Center, College of Medicine, The Catholic University of Korea, 137-701 Seoul, South Korea.
authors.forename: Ha-Jin
authors.initials: HJ
authors.lastname: Pak
authors.affiliation: Department of Anatomy, Catholic Neuroscience Institute, Cell Death Disease Research Center, College of Medicine, The Catholic University of Korea, 137-701 Seoul, South Korea.
authors.forename: Yoo-Jin
authors.initials: YJ
authors.lastname: Shin
authors.affiliation: Department of Anatomy, Catholic Neuroscience Institute, Cell Death Disease Research Center, College of Medicine, The Catholic University of Korea, 137-701 Seoul, South Korea.
authors.forename: Tae-Ryong
authors.initials: TR
authors.lastname: Riew
authors.affiliation: Department of Anatomy, Catholic Neuroscience Institute, Cell Death Disease Research Center, College of Medicine, The Catholic University of Korea, 137-701 Seoul, South Korea.
authors.forename: Joo-Hee
authors.initials: JH
authors.lastname: Park
authors.affiliation: Department of Natural Sciences, College of Medicine, The Catholic University of Korea, 137-701, Seoul, South Korea.
authors.forename: Young Wha
authors.initials: YW
authors.lastname: Moon
authors.affiliation: Department of Anatomy, Catholic Neuroscience Institute, Cell Death Disease Research Center, College of Medicine, The Catholic University of Korea, 137-701 Seoul, South Korea. Electronic address: munylee@catholic.ac.kr.
authors.forename: Mun-Yong
authors.initials: MY
authors.lastname: Lee
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000378:metabolism; D015153:Blotting, Western; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000378:metabolism; D007150:Immunohistochemistry; D002546:Ischemic Attack, Transient / Q000378:metabolism*; D008297:Male; D018613:Microscopy, Confocal; D009474:Neurons / Q000378:metabolism; D020286:Pericytes / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D044169:Receptors, Calcium-Sensing / Q000032:analysis / Q000096:biosynthesis*; D015854:Up-Regulation
chemical_list: D044169:Receptors, Calcium-Sensing; C473605:extracellular calcium cation-sensing receptor, rat
keywords: Corpus striatum; Endothelial cells; Microglia; Pericytes; Reactive astrocytes; Receptors, calcium-sensing; Stroke; Vascular remodeling