Variation in Behavioral Deficits and Patterns of Recovery After Stroke Among Different Rat Strains

Pre-clinical models of stroke therapeutics depend upon the ability to detect differences in infarct volume as well as in the short- and long-term outcomes of treated animals. Little attention has been paid to interstrain differences in these outcomes and the importance of defining the most appropriate behavioral tests. In this study, we evaluate long-term outcome from stroke in three different rat strains. Lewis, Wistar, and Sprague Dawley (SD) rats were subjected to 2-h middle cerebral artery occlusion and survived for up to 49 days. Behavioral tests were performed weekly. There was continuous assessment of rotational/circling activity in the home cage by use of an automated software program. A separate group of animals was sacrificed at 24 h to determine infarct volume. Infarct volume was similar in all three strains. Mortality was significantly higher in SD rats (P < 0.001). Rotational/circling activity at 24 h was correlated with cortical infarct volume in Wistar and SD rats (ρ = 0.67, P = 0.04 and ρ = 0.72, P = 0.01, respectively). Wistar and SD rats displayed more rotational/circling activity following stroke than Lewis rats, but Lewis rats evidenced more impairment on complex motor tasks like the rotarod. Further, computer automated analysis of rotational activity was more sensitive than subjective assessment, with SD rats showing a preference for clockwise rotations to 49 days after stroke despite normalization of the neurological score after 21 days. There are significant interstrain differences in survival and in the patterns of neurological impairment and recovery after stroke. These differences must be taken into account in pre-clinical studies, but may also be capitalized upon to understand genetic contributions to injury. Finally, computerized assessment of behavior is more sensitive than subjective assessment for detecting behavioral changes.