The effect of propofol postconditioning on the expression of K(+)-Cl(-)-co-transporter 2 in GABAergic inhibitory interneurons of acute ischemia/reperfusion injury rats.

Abstract

It has been shown in our previous study that propofol postconditioning enhanced the activity of phosphatidylinositol-3-kinase (PI3K) and prevented the internalization of GluR2 subunit of α-amino-3-hydroxyl-5-methyl-4-isoxazolepropionic acid (AMPA) receptors, thus provided neuroprotection in cerebral ischemia/reperfusion (I/R) injury. Regarding inhibitory system in CNS, K(+)-Cl(-)-co-transporter 2 (KCC2), a Cl(-) extruder, plays a critical role in gamma-aminobutyric acid (GABA) inhibitory effect in mature central neurons. However, the effect of propofol postconditioning on the expression of KCC2 in GABAergic interneurons is unclear. Therefore, in this article we describe the role of KCC2 in GABAergic interneurons in the ipsilateral hippocampal CA1 region of adult rats and the effects of propofol postconditioning on this region. Herein we demonstrate that propofol postconditioning (20mg/kg/h, 2h) improved rats' neurobehavioral abilities, increased the number of survival neurons, and up-regulated neuronal KCC2 expression in glutamic acid decarboxylase 67 (GAD67) expressing GABAergic interneurons in hippocampal CA1 region at 24h after I/R. In contrast, when rats were injected with the KCC2 antagonist, [(dihydroindenyl)oxy] alkanoic acid (DIOA), the neuroprotective effects induced by propofol postconditioning were reversed. Our study indicated that propofol postconditioning increased the expression of KCC2 in inhibitory GABAergic interneurons, thus providing acute neuroprotection to rats who had undergone cerebral I/R injury.

• Authors: Hongbai Wang, Shuying Liu, Haiyun Wang, Guolin Wang, Ai Zhu
• Journal: Brain research (Brain Res) Vol. 1597 Pg. 210-9 (Feb 09 2015) ISSN: 1872-6240 [Electronic] Netherlands
• PMID: 25463027 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Elsevier B.V. All rights reserved.

Chemical References

• ((dihydroindenyl)oxy)alkanoic acid
• Carboxylic Acids
• Indenes
• Neuroprotective Agents
• Symporters
• Glutamate Decarboxylase
• glutamate decarboxylase 1
• Propofol

Topics

• Acute Disease
• Animals
• Brain Ischemia (drug therapy, physiopathology)
• CA1 Region, Hippocampal (drug effects, physiopathology)
• Carboxylic Acids (pharmacology)
• Cell Survival (drug effects)
• Disease Models, Animal
• GABAergic Neurons (drug effects, physiology)
• Glutamate Decarboxylase (metabolism)
• Indenes (pharmacology)
• Infarction, Middle Cerebral Artery
• Interneurons (drug effects, physiology)
• Neuroprotective Agents (pharmacology)
• Propofol (pharmacology)
• Random Allocation
• Reperfusion Injury (drug therapy, physiopathology)
• Stroke (drug therapy, physiopathology)
• Symporters (antagonists & inhibitors, metabolism)
• Treatment Outcome
• K Cl- Cotransporters