Animal models of post-ischemic forced use rehabilitation: methods, considerations, and limitations

Abstract

Many survivors of stroke experience arm impairments, which can severely impact their quality of life. Forcing use of the impaired arm appears to improve functional recovery in post-stroke hemiplegic patients, however the mechanisms underlying improved recovery remain unclear. Animal models of post-stroke rehabilitation could prove critical to investigating such mechanisms, however modeling forced use in animals has proven challenging. Potential problems associated with reported experimental models include variability between stroke methods, rehabilitation paradigms, and reported outcome measures. Herein, we provide an overview of commonly used stroke models, including advantages and disadvantages of each with respect to studying rehabilitation. We then review various forced use rehabilitation paradigms, and highlight potential difficulties and translational problems. Lastly, we discuss the variety of functional outcome measures described by experimental researchers. To conclude, we outline ongoing challenges faced by researchers, and the importance of translational communication. Many stroke patients rely critically on rehabilitation of post-stroke impairments, and continued effort toward progression of rehabilitative techniques is warranted to ensure best possible treatment of the devastating effects of stroke.

Figure 1

Following injury to the forelimb, attempts to use the impaired limb lead to unsuccessful motor attempts. The consequences include pain and failure, creating negative feedback which leads to suppression of the behaviour. Meanwhile, the unaffected or less affected forelimb is used with higher success, leading to reinforced compensation. Together, these constitute the phenomenon of learned non-use. Adapted from Taub et al. [11].

Figure 2

A task-specific reaching exercise can be administered using an apparatus such as this. By piling palatable sugar pellets to one side of the box (opposite from the impaired forelimb) rats are encouraged to use the impaired limb to reach through the center slot. The intensity can be altered by controlling the accessing time, number of pellets, and height of the reaching box.

Figure 3

The Schallert cylinder test [100] is performed by placing the rat into a clear plastic cylinder and analysing the proportion of contralesional limb use during exploring and rearing activities.

Figure 4

The Montoya staircase test [101] measures dexterity and sensorimotor function by analysing pellet reaching behaviour. Rats are placed into apparatus with seven descending steps on each side. Steps are baited with sucrose pellets to encourage reaching.

Figure 5

The horizontal ladder test is used to assess forelimb function when crossing a platform of unevenly spaced rungs. The number of foot slips is determined by video analysis.

Figure 6

Forelimb placing tests involves eliciting a response from either tactile or vibrissae stimulation. Three limbs are held secure while the remaining one is tested for the ability to place the forelimb on the table edge in response to stimulation.