Abstract

BackgroundStroke 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.ResultsNeither LDF nor occlusion times of 45 versus 60 min significantly affected mortality, outcome variability or outcome severity.ConclusionsDue to the unexpectedly high mortality and variability the statistical power was very low and thus the results were inconclusive.

Highlights

  • Stroke is among the leading causes of death and disability

  • In experiment 1, the use of laser Doppler flowmetry (LDF) was evaluated by allocating 40 ovariectomized female rats into two groups, with or without LDF, and 24 h after 60 min of middle cerebral artery occlusion (MCAo) the outcome was assessed by infarct size measurement and a modified sticky tape test

  • We attempted to statistically assess the value of LDF or whether 60 or min of filament-induced middle cerebral artery occlusion are to be recommended if the goal is to minimize mortality and variability, but no firm conclusions can be drawn

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Summary

Introduction

Intense research efforts have provided promising treatment options in animals, most clinical trials in humans have failed and the therapeutic options are few. 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. Intense research efforts have provided increased knowledge about stroke pathophysiology and a multitude of promising treatment strategies in animal models have been suggested [5, 6]. Several factors have been suggested to at least in part explain this apparent translational difficulty, regarding study quality [7]. The problem with low statistical power can be overcome by increasing the group sizes sufficiently, but to adopt such an approach in every study is problematic

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