Photothrombotic Middle Cerebral Artery Occlusion in mice: a novel model of ischemic stroke

Abstract

Stroke is one of the main causes of death and disability worldwide. Over the past decades, several animal models of focal cerebral ischemia have been developed allowing us to investigate pathophysiological mechanisms underlying stroke progression. Despite intense preclinical research efforts, the need for non-invasive mouse models of vascular occlusion targeting the middle cerebral artery yet avoiding mechanical intervention is still pressing. Here, by applying the photothrombotic stroke model to the distal branch of the middle cerebral artery, we developed a novel strategy to induce a targeted occlusion of a large blood vessel in mice. This approach induces unilateral damage encompassing most of the dorsal cortex from the motor up to the visual regions one week after stroke. Pronounced limb dystonia on day one after the damage is partially recovered after one week. Furthermore, we observe the insurgence of blood vessel leakage and edema formation in the periinfarct area. Finally, this model elicits a strong inflammatory response revealed as a strong increase in astrocytes density and morphological complexity in the perilesional region of the cortex compared to both other regions of the ipsilesional and contralesional hemispheres, and sham-operated mice. To conclude, the stroke model we developed induces in mice the light-mediated occlusion of one of the main targets of human ischemic stroke, the middle cerebral artery, free from the limitations of commonly employed preclinical models.

Significant statement

Cerebral ischemic stroke is one of the leading causes of death and disability worldwide. Animal models represent a fundamental benchmark to investigate the pathophysiological mechanisms underlying stroke patients' outcomes. Here, we developed and characterized a novel mouse model of stroke employing the photothrombotic occlusion of the middle cerebral artery, one of the most common injury sites in stroke patients. The light-mediated occlusion leads in the acute phase to a severe motor deficit accompanied by the insurgence of blood-brain barrier extravasation, and the establishment of an inflammatory regime particularly pronounced in the periinfarct cortex. This simple and highly reproducible model faithfully recapitulates human ischemic stroke avoiding common drawbacks of other stroke models.