The Mechanism And Role Of Aquaporin 4 On Tissue Damage And Edema 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 5μl 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.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. Conclusions:These results suggest that AQP4 deletion increases ICH damage, including edema formation, blood-brain barrier damage. Further studies on the protective role of activated AQP4 expression following ICH may provide useful therapeutic target for ICH-induced brain injury. 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 cells death and apoptosis after ICH by using AQP4-/-mice.Methods:ICH was induced by microinjecting 5 u 1 autologous whole blood into the striatum of AQP4+/+ and AQP4-/- mice. We compared cells death and apoptosis rate between AQP4+/+ and AQP4-/- mice following ICH by Nissle staining, TUNEL and Hochest staining. We detected Caspase3, Caspase8, Caspase9, Bax, Bcl2 with Western blot and immunitychemistry. With protein array, we detected expression of cytokine between AQP4+/+ and AQP4-/- mice following ICH, and then, expression of cytokine were tested by Elisa. After injection of IL-1ra, TNFbp, LNMMA and PTIO by ventricle, we detected cells death and apoptosis rate between AQP4+/+ and AQP4-/- mice following ICH by Nissle staining, TUNEL and Hochest staining. we detected IL-1βreceptor and TNF a receptor by Western blot. Eventually, death and apoptotic rate were detected after astrocytes cocultured with IL-1β, TNFα, SNP, LPS.Results:Our experiments showed a significant increase of cells death and apoptosis rate following ICH in AQP4-/- mice, when compared to AQP4+/+ mice following ICH. AQP4 deletion increased Caspase3,Caspase8,Caspase9, Bax expression and inhibited Bcl2 expression following ICH. With antibody array and Elisa techonology, our experiments showed a significant increase of IL-1β, IL-6, IL-12, TNFα, and NO after ICH. AQP4 deletion did not alter expression of IL-1βreceptor and TNFα...