17-AAG post-treatment ameliorates memory impairment and hippocampal CA1 neuronal autophagic death induced by transient global cerebral ischemia.

Abstract

Neuro-inflammation plays an important role in global cerebral ischemia (GCI). The 72-kDa heat shock protein (Hsp70) has been reported to be involved in the inflammatory response of many central nervous system diseases. Preclinical findings implicate that 17-allylamino-demethoxygeldanamycin (17-AAG), an anticancer drug in clinical, provide neuroprotection actions in a rat model of traumatic brain injury, and the beneficial effects of 17-AAG were specifically due to up-regulation of Hsp70. However, no experiments have tested whether 17-AAG has beneficial or harmful effects in the setting of GCI. The present study was designed to determine the hypothesis that administration of 17-AAG could attenuate cerebral infarction and improve neuronal survival, thereby ameliorating memory impairment in a rat model of GCI. Furthermore, to test whether any neuroprotective effect of 17-AAG was associated with inflammatory response and neuronal autophagy, we examined the expression of multiplex inflammatory cytokine levels as well as autophagy-associate protein in hippocampal CA1 of rat brain. Our results showed that post-GCI administration of 17-AAG significantly protected rats against GCI induced brain injury, and 17-AAG is also an effective antagonist of the inflammatory response and thereby ameliorates hippocampal CA1 neuronal autophagic death. We therefore believe that the present study provides novel clues in understanding the mechanisms by which 17-AAG exerts its neuroprotective activity in GCI. All data reveal that 17-AAG might be a potential neuroprotective agent for ischemic stroke.

• Authors: Jianxiong Li, Fei Yang, Jia Guo, Rongrong Zhang, Xiangfeng Xing, Xinyue Qin
• Journal: Brain research (Brain Res) Vol. 1610 Pg. 80-8 (Jun 12 2015) ISSN: 1872-6240 [Electronic] Netherlands
• PMID: 25858486 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Elsevier B.V. All rights reserved.

Chemical References

• Benzoquinones
• Cytokines
• HSP70 Heat-Shock Proteins
• HSP90 Heat-Shock Proteins
• Lactams, Macrocyclic
• Neuroprotective Agents
• Nootropic Agents
• tanespimycin

Topics

• Animals
• Autophagy (drug effects, physiology)
• Benzoquinones (pharmacology)
• CA1 Region, Hippocampal (drug effects, pathology, physiopathology)
• Cytokines (metabolism)
• Disease Models, Animal
• Female
• HSP70 Heat-Shock Proteins (metabolism)
• HSP90 Heat-Shock Proteins (metabolism)
• Ischemic Attack, Transient (drug therapy, pathology, physiopathology, psychology)
• Lactams, Macrocyclic (pharmacology)
• Maze Learning (drug effects, physiology)
• Memory Disorders (drug therapy, pathology, physiopathology)
• Neurons (drug effects, pathology, physiology)
• Neuroprotective Agents (pharmacology)
• Nootropic Agents (pharmacology)
• Random Allocation
• Rats, Sprague-Dawley
• Time Factors