Collagenase-Induced Rat Intra-Striatal Hemorrhage Mimicking Severe Human Intra-Striatal Hemorrhage

Basal ganglia hemorrhage accounts for approximately 50% of all hemorrhagic strokes. A good rat model that produces severe intrastriatal hemorrhage (ISH) mimicking human severe ISH is lacking. The present study compared the intra-striatal injection of 0.2 U with that of 0.6 U of collagenase in inducing severe ISH in rats. Three-Tesla (3T) magnetic resonance imaging (MRI) was used to evaluate brain injuries in terms of hematoma size (volume), midline shift (MLS), and brain edema. This evaluation was further substantiated by determination of behavior and neurologic functions and mortality over 56 h. The 0.2 U collagenase caused hematoma volume increases for 10.3 to 30.1 mm³, while the 0.6 U caused 36.4 to 114.8 mm³, at post-ISH 1 h to 56 h. The 0.6 U collagenase significantly increased MLS to 1.5-3.0 times greater than the 0.2 U did at all post-intracerebral hemorrhage (ICH) time points. The MLS increased dependently with hematoma expansion with high correlation coefficients, yet no mortality occurred. These two dosages, nevertheless, caused the same pattern and severity in relative apparent diffusion coefficient (rADC) changes for three regions of interest (ROIs). Both ISH models induced consistent behavior deficits. The larger dosage produced severe brain injuries as well as neurological deficits, more closely mimicking severe human ISH. Hematoma volume and MLS can be the most useful parameters for evaluating the ISH severity in the present experimental model. The larger dosage, therefore, would be useful for investigating the pathophysiology of the severer ISH in the striatum. This may be applied for evaluating potential therapeutic strategies and outcomes in the future.