Differential expression of the calcium-sensing receptor in the ischemic and border zones after transient focal cerebral ischemia in rats

J Chem Neuroanat. 2015 Jul-Sep:66-67:40-51. doi: 10.1016/j.jchemneu.2015.05.001. Epub 2015 May 23.


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.

Keywords: Corpus striatum; Endothelial cells; Microglia; Pericytes; Reactive astrocytes; Receptors, calcium-sensing; Stroke; Vascular remodeling.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Astrocytes / metabolism
  • Blotting, Western
  • Disease Models, Animal
  • Endothelial Cells / metabolism
  • Immunohistochemistry
  • Ischemic Attack, Transient / metabolism*
  • Male
  • Microscopy, Confocal
  • Neurons / metabolism
  • Pericytes / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Calcium-Sensing / analysis
  • Receptors, Calcium-Sensing / biosynthesis*
  • Up-Regulation


  • Receptors, Calcium-Sensing
  • extracellular calcium cation-sensing receptor, rat