Abstract
Improvement of impaired neurological function(s) is a primary endpoint in experimental stroke recovery studies, making the choice and nature of the functional tests crucial for proper execution and interpretation of such studies. Currently, there are a limited number of neurological tests which reliably evaluate functional deficit in mice over a long period of time after stroke. In this study, we evaluated the applicability of forepaw grip strength and automated von Frey tactile sensitivity tests to assess forelimb dysfunction following stroke in the mouse photothrombotic model and compared them with two widely-used tests, grid-walking and cylinder, for up to 21 days after stroke. Three month-old, CD-1 male mice were randomly subjected to photothrombotic stroke or sham surgery in the sensorimotor cortex (n = 10/group). Neurological assessments were conducted 3 days before and 1, 7, 14 and 21 days after stroke in a blinded manner. Grip strength was measured using Mark-10 digital force gauge at peak tension operation mode and performance of each forepaw to hold a grasped wire was evaluated. In the automated von Frey test, the forelimb withdrawal threshold was measured using the same force gauge, attached to a plastic tip, at peak compression operation mode. The cylinder test was used to determine forelimb symmetry in exploratory rearing in a clear cylinder, whereas the grid-walking test was used to measure the number of forelimb footfaults of mice walking on a metallic grid. Our results indicate that while the length of time required to conduct the two new tests is comparable to that of the grid-walking and cylinder tests, the data from the new tests is obtained and ready for analysis upon completion of the testing session. In addition, our observations indicate that the automated von Frey test detected substantial and sustained deficit in the withdrawal threshold of the mice on all evaluation days after stroke, whereas the forepaw grip strength test was only marginally sensitive to document functional impairment. Our data demonstrate that the automated von Frey tactile sensitivity test is a time efficient and sensitive method which can be used together with other established tests to evaluate long-term functional outcome in the mouse photothrombotic stroke model.