Middle Cerebral Artery Occlusion (MCAO) Model

In the most widely used version, a silicone-coated monofilament is advanced from the carotid artery until it occludes the origin of the middle cerebral artery. The occlusion is either transient, with the filament withdrawn after thirty to ninety minutes to allow reperfusion, or permanent. Outcomes are infarct volume, measured by tetrazolium staining of brain slices or by magnetic resonance imaging at one to three days, together with sensorimotor scoring.

This model produced most preclinical neuroprotection data and also the field's most instructive failure. Dozens of agents that convincingly reduced infarct volume in rodents produced nothing in human trials; the free radical trapping agent NXY-059 is the standard case, effective across animal studies and negative in a large confirmatory trial reported in 2007. The response was a set of methodological recommendations, developed as the STAIR criteria, calling for randomisation, blinded outcome assessment, physiological monitoring, dose-response data, delayed treatment windows, aged and comorbid animals, and replication across laboratories.

The weight to give a positive result follows. Efficacy in young healthy male rodents is a minimum entry requirement, not evidence of clinical benefit, and its value rises only as the design closes the gap to human stroke, which strikes older people with hypertension, diabetes and variable collateral supply.

Two technical points decide whether the headline number means anything. Infarct volume must be corrected for oedema using the contralateral hemisphere, because swelling inflates the measured lesion and an agent that merely reduces oedema looks neuroprotective. And treatment given before or at the moment of occlusion has no clinical counterpart, since no patient is dosed in advance of a stroke.