Post-ischemic hyperglycemia exacerbates the development of cerebral ischemic neuronal damage through the cerebral sodium-glucose transporter

Brain Res. 2012 Dec 13;1489:113-20. doi: 10.1016/j.brainres.2012.10.020. Epub 2012 Oct 15.

Abstract

Post-ischemic hyperglycemia may be one of the triggers of ischemic neuronal damage. However, the detailed mechanisms of this injury process are still unknown. Here, we focused on the involvement of the sodium-glucose transporter (SGLT), which transports glucose together with Na(+) ions, and generates inward currents while transporting glucose into cells, resulting in depolarization and increased excitability. The aim of this study was to determine the involvement of the SGLT in the development of cerebral ischemic stress-induced neuronal damage. Male ddY mice were subjected to 2h of middle cerebral artery occlusion (MCAO). Fasting blood glucose (FBG) was measured using the glucose pilot. Neuronal damage was estimated by histological and behavioral analyses. Phlorizin and glucose were administered by intraperitoneal (i.p.) or intracerebroventricular (i.c.v.) injection. Administration of phlorizin (40, 120 or 200mg/kg, i.p.) significantly and dose-dependently suppressed the elevation of FBG and ischemic neuronal damage. In contrast, phlorizin (10 or 40μg/mouse, i.c.v.) significantly and dose-dependently suppressed ischemic neuronal damage without reducing the elevation of FBG. Moreover, the development of neuronal damage was significantly and dose-dependently exacerbated following i.c.v. administration of glucose (10% or 25% (w/v)), and its exacerbation was suppressed by i.c.v. administration of phlorizin (40μg/mouse). These results suggest that cerebral SGLT is activated by post-ischemic hyperglycemia and may be involved in the exacerbation of ischemic neuronal damage.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Outbred Strains
  • Blood Glucose / drug effects
  • Blood Glucose / metabolism
  • Brain Ischemia / metabolism*
  • Brain Ischemia / pathology
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Glucose / pharmacology
  • Glucose Intolerance / metabolism
  • Glucose Intolerance / pathology
  • Hyperglycemia / metabolism*
  • Hyperglycemia / pathology
  • Infarction, Middle Cerebral Artery / metabolism*
  • Infarction, Middle Cerebral Artery / pathology
  • Injections, Intraperitoneal
  • Injections, Intraventricular
  • Male
  • Mice
  • Neurons / metabolism
  • Neurons / pathology
  • Phlorhizin / pharmacology
  • Sodium-Glucose Transporter 1 / metabolism*
  • Stress, Physiological / physiology

Substances

  • Blood Glucose
  • Slc5a1 protein, mouse
  • Sodium-Glucose Transporter 1
  • Phlorhizin
  • Glucose