Top 3 Behavioral Tests in Cell Therapy Studies After Stroke: Difficult to Stop a Moving Train.

Abstract

Stroke is a huge burden to our society now, and this is expected to grow in the future. The recent stroke burden report in Europe predicts that there will be a 34% increase in the number of stroke cases from 2015 to 2035.1 As a result of improved acute care (eg, thrombolysis, mechanical thrombectomy), more and more patients survive after stroke, but are left with permanent disabilities. One clear unmet medical need is to enhance a functional recovery of stroke patients, and much effort is being expended in devising the so-called restorative therapies, especially those involving stem cells. However, although there is convincing experimental evidence for the benefits of cell therapy, their efficacy remains to be confirmed in human patients.2 The assessment of therapeutic efficacy of cell products in experimental stroke models relies heavily on behavioral testing. There are many behavioral outcome measures available designed to assess gross neurologic deficits, sensorimotor function, and fine skilled movements.3–6 However, there is no consensus about which tests are sensitive for detecting long-term treatment effects or, in general, if there is even an optimal study design for these kinds of stroke recovery studies. Hicks et al7 listed the most frequently used behavioral tests in 2001 to 2009 for assessing the functional outcome after cell-based therapy in experimental stroke. The top 3 were modified neurological severity score (mNSS), adhesive tape removal, and the Rotarod test. The surprising finding was that these frequently used tests most likely to yield positive treatment effects but it is far from clear whether this is because of enhanced motivation, motor learning, or compensation complicating data interpretation. Indeed, these behavioral tasks are simple, requiring minimal manpower, but are also rather likely to be affected by the compensatory strategies developed by stroke animals while completing a …