The Role Of Cathepsin S In Acute Intracerebral Hemorrhage In Mice

Objective1.To find an appropriate dose of collagenase type VⅡ to make a staible model of the acute intracerebral hemorrhage in mice.2. To evaluate the role of the Cathepsin S in the acute intracerebral hemorrhage.Methods1. Male C57BL/6J mice (12-13weeks old) were divided into3groups:high dose (0.075U), medium dose (0.0375U), and low dose (0.01875U). Mortality, neurological deficit score, brain hemorrhagic volume, brain water content, and the number of leukocytes in the hemorrhagic zone were evaluated at24hafter collagenase-induced cerebral hemorrhage in mice of3groups.2. We used wild-type (WT) and Cathepsin S knockout (KO) mice forthe experiments. Experimental intracerebral hemorrhage was induced by the right intrastriatal stereotactic administration of collagenase. Mortality, neurological deficit score, brain hemoglobin content, brain hemorrhagic volume, brain edema, and the number of leukocytes in the hemorrhagic zone at24h after collagenase-induced cerebral hemorrhage were compared between KO and WT mice.Result1. At24h after collagenase-induced cerebral hemorrhage, there was no significant difference of mortality, neurological deficit score, brain hemoglobin content, hematoma volume, and the number of infiltrating leukocytes between high dose and medium dose groups (P>0.05).The mortality rate, brain hemoglobin content, brain hematoma volume, and the number of leukocyte in group of high and medium dose were significantly higher than that of low dose group (P<0.05). The scores of neurological deficit score of the low group was lower when compared with those of high and medium groups, some mice of the low dose group didn’t have any neurological deficit.Mortality was47.8%in the high dose group, the percent of mice having neurological deficit score of4or5was50%, which was much higher than the medium (27.3%) and low dose group (0%).2.24h after collagenase-induced cerebral hemorrhage, there was no significant difference of mortality rate, neurological deficit score, brain hemoglobin content, brain hematoma volume, brain water content, and the number of infiltrating leukocytes between KO and WT mice(P>0.05).Conclusion1. These results indicate that the medium dose is adequate and appropriate for the establishment of the model of acute cerebral hemorrhage in mice. Mortality of this group was very high, so it is not appropriately to be used to make the long term model of cerebral hemorrhage. The low dose group has too little brain injury and it is not appropriate to use low dose of collagense to make acute or long-term model of cerebral hemorrhage.2. Cathepsin S deficiency does not appear to play a important role in the brain damage in the acute collagenase-induced cerebral hemorrhage in mice.