Mouse models of intracerebral hemorrhage in ventricle, cortex, and hippocampus by injections of autologous blood or collagenase.
Intracerebral hemorrhage (ICH) is a devastating condition. Existing preclinical ICH models focus largely on striatum but neglect other brain areas such as ventricle, cortex, and hippocampus. Clinically, however, hemorrhagic strokes do occur in these other brain regions. In this study, we established mouse hemorrhagic models that utilize stereotactic injections of autologous whole blood or collagenase to produce ventricular, cortical, and hippocampal injury. We validated and characterized these models by histology, immunohistochemistry, and neurobehavioral tests. In the intraventricular hemorrhage (IVH) model, C57BL/6 mice that received unilateral ventricular injections of whole blood demonstrated bilateral ventricular hematomas, ventricular enlargement, and brain edema in the ipsilateral cortex and basal ganglia at 72 h. Unilateral injections of collagenase (150 U/ml) caused reproducible hematomas and brain edema in the frontal cortex in the cortical ICH (c-ICH) model and in the hippocampus in the hippocampal ICH (h-ICH) model. Immunostaining revealed cellular inflammation and neuronal death in the periventricular regions in the IVH brain and in the perihematomal regions in the c-ICH and h-ICH brains. Locomotor abnormalities measured with a 24-point scoring system were present in all three models, especially on days 1, 3, and 7 post-ICH. Locomotor deficits measured by the wire-hanging test were present in models of IVH and c-ICH, but not h-ICH. Interestingly, mice in the c-ICH model demonstrated emotional abnormality, as measured by the tail suspension test and forced swim test, whereas h-ICH mice exhibited memory abnormality, as measured by the novel object recognition test. All three ICH models generated reproducible brain damage, brain edema, inflammation, and consistent locomotor deficits. Additionally, the c-ICH model produced emotional deficits and the h-ICH model produced cognitive deficits. These three models closely mimic human ICH and should be useful for investigating the pathophysiology of ICH in ventricle, cortex, and hippocampus and for evaluating potential therapeutic strategies.
Department of Emergency Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, PR China; Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University, School of Medicine, Baltimore, Maryland, United States of America.
Wei
W
Zhu
Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University, School of Medicine, Baltimore, Maryland, United States of America.
Yufeng
Y
Gao
Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University, School of Medicine, Baltimore, Maryland, United States of America.
Che-Feng
CF
Chang
Department of Biological Sciences, Illinois Institute of Technology, College of Science, Chicago, Illinois, United States of America.
Jie-Ru
JR
Wan
Department of Psychiatry and Behavioral Sciences, Johns Hopkins University, School of Medicine, Baltimore, Maryland, United States of America.
Shan-Shan
SS
Zhu
Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University, School of Medicine, Baltimore, Maryland, United States of America.
Jian
J
Wang
D000818:Animals; D001479:Basal Ganglia / Q000473:pathology; D001522:Behavior, Animal; D001804:Blood Transfusion, Autologous; D002540:Cerebral Cortex / Q000473:pathology*; D002543:Cerebral Hemorrhage / Q000473:pathology*; D002552:Cerebral Ventricles / Q000473:pathology*; D017364:Collagenases / Q000009:adverse effects*; D004644:Emotions; D006624:Hippocampus / Q000473:pathology*; D007249:Inflammation; D007276:Injections, Intraventricular; D008124:Locomotion; D008297:Male; D008568:Memory; D051379:Mice; D008810:Mice, Inbred C57BL; D020521:Stroke / Q000503:physiopathology; D013997:Time Factors
D017364:Collagenases