Model of minor stroke with mild peri-infarct ischemic injury

Abstract

Background

Transient ischemic attack, minor stroke and stroke recurrence need improved treatment but lack animal models for research. The aim was to modify photothrombosis methods thereby producing both a minor stroke (with adjacent mild damage) or a minor recurrent stroke.

New method

A minor stroke, as detected using magnetic resonance imaging and histology, was produced using a low intensity beam of white light with a bright centre, a low dose of Rose Bengal and a short 5 min illumination of thinned skull. A recurrent minor stroke was produced by repeating the procedure two days later except the cortical mask was positioned 1.5 mm posteriorly.

Results

The minor photothrombosis procedure produced a small superficial infarct surrounded by a region of scattered necrosis detected histologically. Marked hyperintensities in diffusion weighted and T2 images identified the infarct. Peri-infarct regions with modest T2 increases corresponded to regions of scattered cell death. A recurrent minor photothrombosis produced additional damage in regions with overlapping mild injury.

Comparison with existing methods

Previous photothrombosis methods usually produce large cortical infarcts with little penumbra. The current method produces small infarcts with diffuse mild peri-infarct ischemic injury that can be diagnosed using T2 imaging.

Conclusions

The modified photothrombotic procedure will produce a minor stroke consisting of a small infarct in a region with marked diffusion and T2 hyperintensities and a peri-infarct region of selective necrosis with modest T2 changes. Minor recurrent stroke is readily produced but imaging is key for assessing size and location of each insult.

Abbreviations Dw, diffusion weighted; MRI, magnetic resonance imaging; Iba1, Ionized Calcium-Binding Adapter Molecule 1; T2w, transverse relaxation time weighted; TIA, transient ischemic attack