J Korean Neurosurg Soc.  2007 Jan;41(1):30-38.

The Role of Aquaporin-4 in Cerebral Edema Formation after Focal Cerebral Ischemia in Rats

• Song YJ
• Bae HR
• Ha SU
• Huh JT

Abstract

OBJECTIVE
To elucidate the role of aquaporin-4(AQP4) in cerebral edema formation, we studied the expression and subcellular localization of AQP4 in astrocytes after focal cerebral ischemia.
METHODS
Cerebral ischemia were induced by permanent middle cerebral artery(MCA) occlusion in rats and estimated by the discoloration after triphenyltetrazolium chloride(TTC) immersion. Change of AQP4 expression were evaluated using western blot. Localization of AQP4 was assessed by confocal microscopy and its interaction with alpha-syntrophin was analyzed by immunoprecipitation.
RESULTS
After right MCA occlusion, the size of infarct and number of apoptotic cells increased with time. The ratio of GluR1/GluR2 expression also increased during ischemia. The polarized localization of AQP4 in the endfeet of astrocytes contacting with ventricles, vessels and pia mater was changed into the diffuse distribution in cytoplasm. The interactions of AQP4 and Kir with alpha-syntrophin, an adaptor of dystrophin complex, were disrupted by cerebral ischemia.
CONCLUSION
The deranged spatial buffering function of astrocytes due to mislocalized AQP4/Kir4.1 channel as well as increased assembly of Ca2+ permeable AMPA receptors might contribute to the development of edema formation and the excitotoxic neuronal cell death during ischemia.

Keyword

Brain edema; Cerebral infarction; Aquaporin 4; KIR receptors; alpha-syntrophin; Apoptosis

MeSH Terms

Animals
Apoptosis
Aquaporin 4
Astrocytes
Blotting, Western
Brain Edema*
Brain Ischemia*
Cell Death
Cerebral Infarction
Cytoplasm
Dystrophin
Edema
Immersion
Immunoprecipitation
Ischemia
Microscopy, Confocal
Neurons
Pia Mater
Rats*
Receptors, AMPA
Receptors, KIR
Aquaporin 4
Dystrophin
Receptors, AMPA
Receptors, KIR