Inhibition of ischaemic tolerance in the gerbil hippocampus by quercetin and anti-heat shock protein-70 antibody.
To clarify the role of heat shock protein-70 (HSP70) in ischaemic tolerance following pretreatment with sublethal cerebral ischaemia, we examined whether the induction of tolerance in the gerbil hippocampus is inhibited by quercetin, an inhibitor of HSP70 expression, or anti-HSP70 antibody. A 3 min period of forebrain ischaemia was induced following pretreatment with 2 min of ischaemia and 3 days of reperfusion. Quercetin or anti-HSP70 antibody was continuously infused into the left lateral ventricle using an implanted osmotic minipump started 3 h after or 2 h before the first ischaemia. The animals were killed 4 days after the second ischaemia for histological observations. Both agents produced no neuronal damage in the brain following a single 2 min period of ischaemia. The neuronal density of the CA1 hippocampus in animals subjected to treatment with quercetin and anti-HSP70 antibody was significantly lower than vehicle-treated animals but were significantly higher than animals with a single 3 min period of ischaemia. Thus, the present study showed that quercetin and anti-HSP70 antibody prevent the induction of ischaemic tolerance. The result suggests that HSP70 expression, at least in part, plays a role in the induction of ischaemic tolerance.
Nakata
N
N
Department of Neurology, Tohoku University School of Medicine, Sendai, Japan.
Kato
H
H
Kogure
K
K
D000818:Animals; D000906:Antibodies / Q000276:immunology; D002545:Brain Ischemia / Q000503:physiopathology*; D005849:Gerbillinae; D006360:Heat-Shock Proteins / Q000276:immunology*; D006624:Hippocampus / Q000503:physiopathology*; D008297:Male; D009474:Neurons / Q000502:physiology; D011794:Quercetin / Q000494:pharmacology*
D000906:Antibodies; D006360:Heat-Shock Proteins; D011794:Quercetin