A new method for preparing a rat intracerebral hemorrhage model by combining focused ultrasound and microbubbles

Abstract

Background: We aimed to prepare a non-invasive, reproducible, and controllable rat model of intracerebral hemorrhage with focused ultrasound (FUS).

Methods: A rat intracerebral hemorrhage (ICH) model was established by combining FUS and microbubbles (μBs), and edaravone was used to verify whether the free radical scavenger had a protective effect on the model. The brain tissue of each group was sectioned to observe the gross histology, blood-brain barrier (BBB) permeability, cerebral infarction volume, and histopathological changes.

Results: Compared with the FUS group, the BBB permeability was significantly increased in the FUS + μBs (F&B) group (p = 0.0021). The second coronal slice in the F&B group had an obvious hemorrhage lesion, and the FUS + μBs + edaravone (F&B&E) group had smaller hemorrhage areas; however, ICH did not occur in the FUS group. The cerebral infarction volume in the F&B group was significantly larger than that in the FUS group (p = 0.0030) and F&B&E group (p = 0.0208). HE staining results showed that nerve fibrinolysis, neuronal necrosis, microglia production, and erythrocytes were found in both the F&B group and the F&B&E group, but the areas of the nerve fibrinolysis and neuronal necrosis in the F&B group were larger than the F&B&E group.

Conclusions: A rat ICH model was successfully prepared using the μBs assisted FUS treatment, and edaravone had a therapeutic effect on this model. This model can be used to study the pathophysiological mechanism of ICH-related diseases and in preclinical research on related new drugs.

Keywords: ICH model; focused ultrasound (FUS); microbubbles (μBs); rat.