Effect of laser Doppler flowmetry and occlusion time on outcome variability and mortality in rat middle cerebral artery occlusion: inconclusive results

Edvin Ingberg, Hua Dock, Elvar Theodorsson, Annette Theodorsson, Jakob O. Ström

Stroke is among the leading causes of death and disability. Although intense research efforts have provided promising treatment options in animals, most clinical trials in humans have failed and the therapeutic options are few. Several factors have been suggested to explain this translational difficulty, particularly concerning methodology and study design. Consistent infarcts and low mortality might be desirable in some, but not all, studies. Here, we aimed to investigate whether the use of laser Doppler flowmetry (LDF) and the occlusion time (60 vs. 45 min) affected outcome variability and mortality in a rat stroke model. Eighty ovariectomized female Wistar rats were subjected to ischemic stroke using intraluminal filament middle cerebral artery occlusion with or without LDF and with occlusion times of 45 or 60 min. Outcome was evaluated by triphenyl tetrazolium chloride staining of brain slices to measure infarct size and a modified sticky tape test. Neither LDF nor occlusion times of 45 versus 60 min significantly affected mortality, outcome variability or outcome severity. Due to the unexpectedly high mortality and variability the statistical power was very low and thus the results were inconclusive.