Mouse Models of Intracerebral Hemorrhage in Ventricle, Cortex, and Hippocampus by Injections of Autologous Blood or Collagenase

Abstract

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.

Angiotensin-(1–7) counteracts the effects of Ang II on vascular smooth muscle cells, vascular remodeling and hemorrhagic stroke: Role of the NFкB inflammatory pathway

“…At 24 hrs after ICH induction, neurological deficit scores (NDS) were determined by using a 24-point scoring system [22, 23], including body symmetry, gait, climbing, circling behavior, front limb symmetry, and compulsory circling. Each test was graded from 0 to 4, establishing a maximum deficit score of 24.…”

Intracerebral haemorrhage-induced injury progression assessed by cross-sectional photoacoustic tomography

“…Brain tissue loss is common in ICH models [29,32]. Histology results in previous studies showed that tissue loss and brain atrophy occured in several brain regions, including cortex [29] and striatum [37].…”

“…Each test was graded from 0 to 4, providing a total score of 0 to 24, with higher scores indicative of greater neurologic injury [29,31,32].…”

Wharton’s Jelly Transplantation Improves Neurologic Function in a Rat Model of Traumatic Brain Injury

“…Coronal cryostat sections 400μm apart between bregma -0.5 mm and bregma -4.5mm were stained with hematoxylin and eosin. Image J software (NIH, Bethesda, MD, USA) was used to quantify lesion volumes (Zhu et al 2014). The volume of the lesion in cubic millimeters was calculated as the sum of the damaged areas of each section multiplied by the interslice distance (Wu et al 2012).…”

“…We compared the total time spent exploring the old and new objects. The exploration time included time in direct contact with the object and time within the object area; a discrimination index (total time spent with new object/total time devoted to exploration of objects) was also calculated for each rat (Zhu et al 2014). …”