Translational Stroke Research

, Volume 2, Issue 2, pp 195–201

Mild Hypothermia Suppresses Calcium-Sensing Receptor (CaSR) Induction Following Forebrain Ischemia While Increasing GABA-B Receptor 1 (GABA-B-R1) Expression

Authors

  • Jong Youl Kim
    • Department of NeurologyUniversity of California, San Francisco and Veterans Affairs Medical Center
    • Department of MedicineUniversity of California, San Francisco and Veterans Affairs Medical Center
  • Nuri Kim
    • Department of NeurologyUniversity of California, San Francisco and Veterans Affairs Medical Center
    • Department of NeurologyUniversity of California, San Francisco and Veterans Affairs Medical Center
  • Wenhan Chang
    • Department of MedicineUniversity of California, San Francisco and Veterans Affairs Medical Center
Original Article

DOI: 10.1007/s12975-011-0082-4

Cite this article as:
Kim, J.Y., Kim, N., Yenari, M.A. et al. Transl. Stroke Res. (2011) 2: 195. doi:10.1007/s12975-011-0082-4

Abstract

Hypothermia improves neurological outcome from cardiac arrest. The mechanisms of protection are multifold, but identifying some may be useful in exploring potential therapeutic targets. The extracellular calcium-sensing receptor (CaSR) was originally found in parathyroid cells in which the receptor senses minute changes in extracellular [Ca2+] and promotes Ca2+ influx and intracellular Ca2+ release. The CaSR is broadly expressed in the CNS and colocalized with the inhibitory γ-aminobutyric acid-B receptor 1 (GABA-B-R1). In hippocampal neurons, GABA-B-R1 heterodimerizes with CaSR and suppresses CaSR expression. To study the interplay between these two receptors in the development of ischemic cell death and neuroprotection by hypothermia, we subjected C57/BL6 mice to global cerebral ischemia by performing bilateral carotid artery occlusion (10 min) followed by reperfusion for 1–3 days with or without therapeutic hypothermia (33°C for 3 h at the onset of reperfusion). Terminal deoxynucleotidyl transferase dUTP nick end labeling staining and immunohistochemistry showed that forebrain ischemia increased CaSR expression, decreased GABA-B-R1 expression, and promoted cell death. These changes were particularly evident in hippocampal neurons and could be reversed by mild hypothermia. The induction of CaSR, along with reciprocal decreases in GABA-B-R1 expression, may together potentiate ischemic neuronal death, suggesting a new therapeutic target for treatment of ischemic brain injury.

Keywords

Calcium-sensing receptorGlobal cerebral ischemiaHypothermiaNeuroprotection

Copyright information

© Springer Science+Business Media, LLC 2011