Intranasal administration of collagenase develops cerebral microbleeds and vascular dementia in mice: In vivo pilot study

Objective

To establish a new animal model of lobar cerebral microbleeds (CMBs), we examined whether intranasal administration of collagenase induced CMBs in young mice which did not have hypertensive pathologic features.

Methods

We used thirty-two male CD1 mice (8–10 weeks old), which were received either phosphate-buffered saline (PBS) or collagenase by intranasal administration twice a day for 5 days. A dose response study was conducted, and motor function and number of CMBs was evaluated at one day after completing the intranasal administration. Temporal profile of cognitive impairment and number of CMBs through 7 days was evaluated after completing intranasal administration of 3.6U collagenase.

Results

The number of CMBs showed an increasing trend in a dose-dependent manner and higher number of CMBs were observed with 3.6U collagenase. Cognitive impairment and CMBs was observed in 3.6U collagenase groups up to 7 days after administration. In addition, successful brain delivery via intranasal route was comfirmed by administering fluorescein isothiocyanate-labeled bovine serum albumin.

Conclusions

Intranasal collagenase administration is a feasible and minimally invasive method to produce CMBs and cognitive impairment in mice. This model has potential for producing CMBs in animals with cerebral amyloid angiopathy such as transgenic mice models of Alzheimer’s disease.