Expression of interleukin-6 is suppressed by inhibition of voltage-sensitive Na+/Ca2+ channels after cerebral ischemia

Neuroreport. 2000 Aug 3;11(11):2565-9. doi: 10.1097/00001756-200008030-00043.

Abstract

Expression of interleukin-6 (IL-6), a neurotrophic cytokine, is up-regulated after cerebral ischemia, but the underlying mechanism of the up-regulation remains unclear. NS-7 is a novel blocker of voltage-sensitive Ca2+ and Na+ channels and is known to reduce cerebral damage by ischemia. The present study was undertaken to examine the association between increases in intracellular Ca2+ concentration induced by membrane depolarization and IL-6 induction. IL-6 expression in rat brain was investigated by immunohistochemistry and Western blot analysis following 3.5-48 h of reperfusion after 1.5 h of occlusion of the middle cerebral artery. NS-7 (1 mg/kg; NS-7 group) or saline (saline group) was injected i.v. 5 min after the start of reperfusion. The saline group showed clear IL-6 expression in various cortical regions, which peaked at 24 h of reperfusion. By contrast, IL-6 expression was significantly suppressed in the NS-7 group throughout the reperfusion period. Microglia activation was also reduced in the NS-7 group. These findings suggest that IL-6 expression may be up-regulated by the increased intracellular Ca2+ concentration triggered by membrane depolarization after cerebral ischemia.

MeSH terms

  • Animals
  • Brain / drug effects
  • Brain / metabolism*
  • Brain / physiopathology
  • Brain Ischemia / drug therapy
  • Brain Ischemia / metabolism*
  • Brain Ischemia / physiopathology
  • Calcium Channels / drug effects
  • Calcium Channels / metabolism*
  • Interleukin-6 / metabolism*
  • Male
  • Nerve Degeneration / metabolism
  • Nerve Degeneration / pathology
  • Nerve Degeneration / physiopathology
  • Neurons / drug effects
  • Neurons / metabolism
  • Neurons / pathology
  • Neuroprotective Agents / pharmacology
  • Pyrimidines / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Reperfusion Injury / drug therapy
  • Reperfusion Injury / metabolism*
  • Reperfusion Injury / physiopathology
  • Sodium Channels / drug effects
  • Sodium Channels / metabolism*

Substances

  • 4-(4-fluorophenyl)-2-methyl-6-(5-piperidinopentyloxy)pyrimidine hydrochloride
  • Calcium Channels
  • Interleukin-6
  • Neuroprotective Agents
  • Pyrimidines
  • Sodium Channels