The Establishing And Evaluation Of Intracerebral Hemorrhage Mouse Model And Relationship Research Between Aquaporin 4 And Brain Damage Following Intracerebral Hemorrhage

Part I The establishing and evaluation of intracerebral hemorrhage mouse modelObjective:Establishing and Evaluation the caudate nucleus auto-whole blood injection cerebral hemorrhage mouse model.Methods:144 male ICR mice were randomly divided into 3 groups(10ul group,30ul group,sham),each group's survival rate was determined at 8h (n=8),24h (n=8),48h (n=8),72h (n=8),120h (n=8),and 168h (n=8) after modeling; 108 male ICR mice were randomly divided into 3 groups(10ul group,30ul group,sham),each group's neurologic impairment and brain water content were determined at 8h (n=8),24h (n=8),48h (n=8),72h (n=8),120h (n=8),and 168h (n=8) after modeling; 144 male ICR mice were randomly divided into 3 groups(10ul group,30ul group,sham),each group's brain specimen were perfusion to HE and Nissl's staining.Results:The 7 days'mortalitys were significantly different between lOul group and 30ul group;the neurologic impairment and brain water content were significantly different between modeling groups and sham groups;Longa score and Bederson score were related with lOul group's mortality,manual muscle test and forelimb were related with 30ul group's mortality.Conclusions:Mice autologous blood isecondary injection model is a convenient and reliable model of cerebral hemorrhage;for different experimental purposes, you can choose different methods of behavioral score. PartⅡThe relationship research between Aquaporin 4 and brain damage following intracerebral hemorrhageObjective: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 AQP-4 (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 AQP-4 in edema formation after ICH by using AQP-4-/-mice.Methods:ICH was induced by microinjecting 5μl autologous whole blood into the striatum of AQP-4+/+and AQP-4-/-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 AQP-4+/+ and AQP-4-/- mice following ICH. Histological changes were also detected with Nissl's staining and TUNEL staining.Results:Our experiments showed a significant increase of AQP-4 expression following ICH in AQP-4+/+ mice. AQP-4 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 AQP-4-/-mice following ICH.Conclusions:These results suggest that AQP-4 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 AQP-4 expression following ICH may provide useful therapeutic target for ICH-induced brain injury.