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Murine brain histological analysis

Claudio Maderna

CellPress - STAR Protocols


Murine brain is a different way to define what we normally call "mouse brain"; which can be affected from Cavernomas.

Cavernomas are multi-lumen and blood-filled vascular malformations which form in the brain and the spinal cord.

They lead to hemorrhage, epileptic seizures, neurological deficits, and paresthesia.

An effective medical treatment is still lack-ing, and the available murine models for cavernomas have several limitations for preclinical studies.

These include disease phenotypes that differ from human dis-eases, such as restriction of the lesions to the cerebellum, and absence of acute

Additional limitations of current murine models include rapid devel-opment of lesions, which are lethal before the first month of age.

Here, we have characterized a murine model that recapitulates features of the human disease.

Lesions develop after weaning throughout the entire CNS, including the spinal
cord, and undergo acute hemorrhage.

This provides a preclinical model to develop new drugs for treatment of acute hemorrhage in the brain and spinal cord, as an unmet medical emergency for patients with cavernomas.

In the study of cerebral cavernous malformations (CCMs), the quantification of lesion burden is the main parameter for evaluation of disease severity and efficacy of drugs.

We describe a reliable and cost-effective protocol to evaluate the number and the size of vascular malformations in the murine brain.

This approach is based on histology and confocal imaging and can be performed with standard laboratory equipment.


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