MRI-based analysis of intracerebral hemorrhage in mice reveals relationship between hematoma expansion and the severity of symptoms

PLoS One. 2013 Jul 2;8(7):e67691. doi: 10.1371/journal.pone.0067691. Print 2013.


Intracerebral hemorrhage (ICH) is featured by poor prognosis such as high mortality rate and severe neurological dysfunction. In humans, several valuables including hematoma volume and ventricular expansion of hemorrhage are known to correlate with the extent of mortality and neurological dysfunction. However, relationship between hematoma conditions and the severity of symptoms in animal ICH models has not been clarified. Here we addressed this issue by using 7-tesla magnetic resonance imaging (MRI) on collagenase-induced ICH model in mice. We found that the mortality rate and the performance in behavioral tests did not correlate well with the volume of hematoma. In contrast, when hemorrhage invaded the internal capsule, mice exhibited high mortality and showed poor sensorimotor performance. High mortality rate and poor performance in behavioral tests were also observed when hemorrhage invaded the lateral ventricle, although worsened symptoms associated with ventricular hemorrhage were apparent only during early phase of the disease. These results clearly indicate that invasion of the internal capsule or the lateral ventricle by hematoma is a critical determinant of poor prognosis in experimental ICH model in mice as well as in human ICH patients. MRI assessment may be a powerful tool to refine investigations of pathogenic mechanisms and evaluations of drug effects in animal models of ICH.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cerebral Hemorrhage / chemically induced
  • Cerebral Hemorrhage / mortality
  • Cerebral Hemorrhage / pathology*
  • Collagenases / adverse effects
  • Disease Progression
  • Hematoma / chemically induced
  • Hematoma / mortality
  • Hematoma / pathology*
  • Humans
  • Injections, Intraventricular
  • Internal Capsule / drug effects
  • Internal Capsule / pathology*
  • Lateral Ventricles / drug effects
  • Lateral Ventricles / pathology*
  • Magnetic Resonance Imaging
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Psychomotor Performance / drug effects
  • Severity of Illness Index
  • Survival Analysis


  • Collagenases

Grant support

This work was supported by The Smoking Research Foundation, Mitsubishi Pharma Research Foundation, MEXT KAKENHI Grant Number 23117714, and JSPS KAKENHI Grant Number 24659118. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. One of the funders (Mitsubishi Pharma Research Foundation) is based on commercial source, but this does not alter the authors' adherence to all the PLOS ONE policies on sharing data and materials. The authors have no relation with this foundation concerning employment, consultancy, patents, products in development or marketed products etc.