Open Accessp53‐Induced Uncoupling Expression of Aquaporin‐4 and Inwardly Rectifying K + 4.1 Channels in Cytotoxic Edema after Subarachnoid Hemorrhage
Author(s) -
Yan Junhao,
Khatibi Nikan H.,
Han Hongbin,
Hu Qin,
Chen Chunhua,
Li Li,
Yang Xiaomei,
Zhou Changman
Publication year - 2012
Publication title -
cns neuroscience and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 69
eISSN - 1755-5949
pISSN - 1755-5930
DOI - 10.1111/j.1755-5949.2012.00299.x
Subject(s) - aquaporin 4 , western blot , astrocyte , subarachnoid hemorrhage , cytotoxic t cell , immunohistochemistry , medicine , edema , pharmacology , perforation , pathology , chemistry , anesthesia , biochemistry , central nervous system , in vitro , punching , materials science , metallurgy , gene
SUMMARY Aims: To investigate the mechanism behind cytotoxic edema formation following subarachnoid hemorrhage (SAH). Methods: We explored the role of aquaporin‐4 (AQP4), inwardly rectifying K + 4.1 (Kir4.1) channels and their upstream orchestrators p53 and p38MAPK in this process. A p53 inhibitor, pifithrin‐α (PFT‐α) was administered intraperitoneally to rats undergoing SAH by endovascular perforation. Totally, 98 male SD rats were categorized into sham, SAH, SAH+ dimethyl sulfoxide (DMSO), SAH+ 0.2 or 2.0 mg/kg PFT‐α groups. At 24 h after SAH, MRI (diffusion‐weighted imaging [DWI]), immunohistochemistry, and Western blot were used. Results: MRI (DWI) showed a significant cytotoxic edema in the brain following SAH with PFT‐α therapy reducing it. Immunohistochemistry and Western blot showed an increased level of p53, phosphorylated‐p38MAPK and AQP4 and a reduced level of Kir4.1; all of which could be reversed following PFT‐α treatment. Treble labeling staining revealed colocalization of p53 with phosphorylated‐p38MAPK and unmatched expression of AQP4 and Kir4.1 within astrocyte cells. Conclusion: These results indicated p53 mediates the formation of cytotoxic edema in the brain following SAH; an uncoupling expression of AQP4 and Kir4.1 on astrocytic end feets orchestrated by p38MAPK was partly responsible.