title: 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.affiliation: Department of Anesthesiology, Tianjin Medical University General Hospital, Tianjin Research Institute of Anesthesiology, Tianjin, People׳s Republic of China.
authors.forename: Hongbai
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Anesthesiology, Tianjin Medical University General Hospital, Tianjin Research Institute of Anesthesiology, Tianjin, People׳s Republic of China.
authors.forename: Shuying
authors.initials: S
authors.lastname: Liu
authors.affiliation: Department of Anesthesiology, Tianjin Medical University General Hospital, Tianjin Research Institute of Anesthesiology, Tianjin, People׳s Republic of China. Electronic address: wanghy819@hotmail.com.
authors.forename: Haiyun
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Anesthesiology, Tianjin Medical University General Hospital, Tianjin Research Institute of Anesthesiology, Tianjin, People׳s Republic of China.
authors.forename: Guolin
authors.initials: G
authors.lastname: Wang
authors.affiliation: Department of Anesthesiology, Tianjin Medical University General Hospital, Tianjin Research Institute of Anesthesiology, Tianjin, People׳s Republic of China.
authors.forename: Ai
authors.initials: A
authors.lastname: Zhu
mesh_terms: D000208:Acute Disease; D000818:Animals; D002545:Brain Ischemia / Q000188:drug therapy* / Q000503:physiopathology; D056547:CA1 Region, Hippocampal / Q000187:drug effects / Q000503:physiopathology; D002264:Carboxylic Acids / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D004195:Disease Models, Animal; D059330:GABAergic Neurons / Q000187:drug effects / Q000502:physiology; D005968:Glutamate Decarboxylase / Q000378:metabolism; D007192:Indenes / Q000494:pharmacology; D020244:Infarction, Middle Cerebral Artery; D007395:Interneurons / Q000187:drug effects* / Q000502:physiology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D015742:Propofol / Q000494:pharmacology*; D011897:Random Allocation; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000503:physiopathology; D020521:Stroke / Q000188:drug therapy / Q000503:physiopathology; D027981:Symporters / Q000037:antagonists & inhibitors / Q000378:metabolism*; D016896:Treatment Outcome; D000096922:K Cl- Cotransporters
chemical_list: D002264:Carboxylic Acids; D005968:Glutamate Decarboxylase; D007192:Indenes; D018696:Neuroprotective Agents; D015742:Propofol; D027981:Symporters; D000096922:K Cl- Cotransporters; C059990:((dihydroindenyl)oxy)alkanoic acid; C402565:glutamate decarboxylase 1
keywords: Cerebral ischemia/reperfusion injury; DIOA; GABAergic interneurons; GAD67; K(+)-Cl(-)-co-transporter (KCC2); Propofol postconditioning