Effects of Aquaporin-4 on edema formation following intracerebral hemorrhage.
OBJECTIVE
Intracerebral hemorrhage (ICH) constitutes 10% to 15% of all strokes and is associated with high morbidity and mortality. To date, little is known about the role of AQP4 (Aquaporin-4), which is abundantly expressed in pericapillary astrocyte foot processes and in edema formation after intracerebral hemorrhage. The purpose of this study was to examine the role of AQP4 in edema formation after ICH by using AQP4(-/-) mice.


METHODS
ICH was induced by microinjecting 5microl autologous whole blood into the striatum of AQP4(+/+) and AQP4(-/-) mice. We compared neurological deficits, brain edema contents of whole hemorrhagic ipsilateral hemisphere, specific gravity of brain tissue surrounding hematoma, Evans blue leakage and ultrastructure of brain microvessels between AQP4(+/+) and AQP4(-/-) mice following ICH. Histological changes were also detected with Nissl's staining and TUNEL staining.


RESULTS
Our experiments showed a significant increase of AQP4 expression following ICH in AQP4(+/+) mice. AQP4 deletion aggravated neurological deficits and brain edema contents of whole hemorrhagic ipsilateral hemisphere. Besides, it also reduced the specific gravity of brain tissue surrounding hematoma. Moreover, it enhanced Evans blue leakage and ultrastructure of brain microvessel damage. Histology also showed less Nissl's staining and more TUNEL staining in AQP4(-/-) mice following ICH.


CONCLUSIONS
These results suggest that AQP4 deletion increases ICH damage, including edema formation, blood-brain barrier damage and neuronal death/TUNEL-positive cells. Further studies on the protective role of activated AQP4 expression following ICH may provide useful therapeutic target for ICH-induced brain injury.
Department of Neurology, Huashan Hospital, Fudan University, Shanghai, China.
Yuping
Y
Tang
Pin
P
Wu
Jinjin
J
Su
Jun
J
Xiang
Dingfang
D
Cai
Qiang
Q
Dong
D000818:Animals; D051401:Aquaporin 4 / Q000235:genetics* / Q000378:metabolism*; D001812:Blood-Brain Barrier / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D001929:Brain Edema / Q000378:metabolism* / Q000473:pathology*; D016923:Cell Death; D002543:Cerebral Hemorrhage / Q000378:metabolism* / Q000473:pathology*; D003342:Corpus Striatum / Q000378:metabolism / Q000473:pathology; D005455:Fluorescent Antibody Technique; D020287:In Situ Nick-End Labeling; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008854:Microscopy, Electron; D013046:Specific Gravity; D020521:Stroke / Q000378:metabolism / Q000473:pathology; D019108:Tight Junctions / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D014867:Water / Q000378:metabolism
C496031:Aqp4 protein, mouse; D051401:Aquaporin 4; D014867:Water