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

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.

• Authors: S Suzuki, K Tanaka, S Nogawa, T Dembo, A Kosakai, Y Fukuuchi
• Journal: Neuroreport (Neuroreport) Vol. 11 Issue 11 Pg. 2565-9 (Aug 03 2000) ISSN: 0959-4965 [Print] England
• PMID: 10943723 (Publication Type: Journal Article)

Chemical References

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

Topics

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