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Stroke. 2010 Mar;41(3):e151-9. doi: 10.1161/STROKEAHA.109.570424. Epub 2009 Dec 31.

Downregulation of potassium chloride cotransporter KCC2 after transient focal cerebral ischemia.

Author information

1
Hans-Berger Clinic for Neurology, Friedrich-Schiller University, Erlanger Allee 101, 07747 Jena, Germany. christiane.frahm@med.uni-jena.de

Abstract

BACKGROUND AND PURPOSE:

The potassium chloride cotransporter 2 (KCC2) is the main neuronal chloride extruder in the adult nervous system. Therefore, KCC2 is responsible for an inwardly directed electrochemical gradient of chloride that leads to hyperpolarizing GABA-mediated responses. Under some pathophysiological conditions, GABA has been reported to be depolarizing because of a downregulation of KCC2. This is the first study to our knowledge analyzing the expression of KCC2 after a focal cerebral ischemia.

METHODS:

Mild and severe ischemia were induced in rats by a transient occlusion of the middle cerebral artery for 30 and 120 minutes, respectively. KCC2 mRNA and protein expression were studied in the ischemic hemisphere after different reperfusion times (2 hour, 1 day, 7 days, 30 days, 168 days) by using quantitative polymerase chain reaction, Western blotting, and immunohistological staining.

RESULTS:

We found a substantial decrease of KCC2 mRNA and protein levels in the ischemic hemisphere, with a stronger downregulation of KCC2 after severe vs mild ischemia. Long-term surviving cells expressing KCC2 could be detected in the infarct core. These cells were identified as GABAergic interneurons mainly expressing parvalbumin.

CONCLUSIONS:

Our study revealed a substantial neuron-specific downregulation of KCC2 after focal cerebral ischemia.

PMID:
20044519
DOI:
10.1161/STROKEAHA.109.570424
[Indexed for MEDLINE]
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