コラゲナーゼ脳内出血モデル

Abstract

In contrast to cerebral ischemia, there have been few experimental sdudies on intracerebral hemorrhage (ICH), alth6ugh ICH is one of the most important cerebral vascular diseases, as much so as cerebral infarction. In 1990, Rosenberg and coworkers developed an elegant rat model in which intrastriatal injection of bacterial collagenase causes bleeding into the brain tissue. This model is considered to be a reproducible method to induce a hematoma and to regulate its size depending on the amount of collagenase injected. But this reproducibility has never been discussed ; we made a modified collagenase induced ICH model in order to verify the reliability of this model. A total 56 of adult male rats were studied. 2μl artificial cerebropinal fluid, which was adjusted to a pH 7.4 by buffer, containing 0.25 unit bacterial collagenase was stereo- tactically injected into the left caudoputamen in 28 rats. The remaining 28 rats were injected with 0.5 unit bacterial collagenase under the same procedure. Volumetry was performed at 2, 4, 12, 24, 48, 168, and 720 hours after injection to compare the difference between groups and observe the natural history of the hematoma. At 4 hours after injection there was a marked hematoma within the caudoputamen which stopped developing in size by 24 hours. At 24 hours, 0.25 unit collagenase caused 60μl hematoma and 0.5 unit collagenase caused 100μl hematoma. At 1 week, the hematoma was resolving and reduced the size to 35% of the maximum value. At 1 month, the hematoma represented a slit-like appearance accompanying the atrophy of ipsilateral hemisphere. The hematoma of 0.5 unit collagenase was significantly larger than that of 0.25 unit collagenase for the entire experimental period. But there was no difference between the groups concerning the time course of hematoma. We conclude that our modified collagenase induced ICH model is quite reproducible and most suitable for the study of ICH. This model should therefore be used for further investigation of ICH.