Behavioral Testing in Rodent Models of Stroke
The critical test of a therapeutic intervention is whether it affects clinically relevant outcomes. Reliable tests of functional outcome, therefore, represent a vital part of preclinical stroke research. This chapter presents select behavioral tests commo
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1. Introduction Behavioral tests are essential components of preclinical research in rodent models of focal ischemic or hemorrhagic stroke. A comprehensive behavioral assessment may require a rather extensive battery of tests with each test describing the specific aspects of behavior. There is no static test battery that could be recommended for animal models of stroke. Rather, existing test batteries are constantly being modified to address the demands of particular experiments. At a minimum, a useful test battery comprises tests that are sensitive to the type and severity of deficits predicted after the injury. Each of the tests provides graded outcome in response to a therapeutic intervention chronically after injury and is not much influenced by repeated testing. To expedite research,
Ulrich Dirnagl (ed.), Rodent Models of Stroke, Neuromethods, vol. 47, DOI 10.1007/978-1-60761-750-1_14, © Springer Science+Business Media, LLC 2010
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each test produces a number of measurements, such as a combination of observational descriptions along with end point measures. There are some practical considerations that determine the choice of test. As compared to complex scoring systems, rather simple scores may be easy to use, yet the outcome may not display small differences between graded levels of injury or subtle therapeutic effects. Other tests may require habituation to the test apparatus or pretraining prior to testing, which will then allow for longitudinal testing once habituation or training is completed. Furthermore, measuring quantitative (end point) along with qualitative (descriptive) data will help dissociate mechanisms of improvement through brain repair versus behavioral compensation. Learned compensatory behaviors may develop through repeated testing and lead to false conclusions about the efficacy of an intervention. The following chapter will not attempt to provide an allinclusive review of the numerous behavioral tests available. It will rather introduce select tests that can be used to create a reliable test battery for the assessment of typical sensory, motor and cognitive deficits in rodent models of stroke. Although some of the tests have been used mainly in rats, the training and test protocols described can easily be adapted for use in other rodents. Further details can be found in the cited methods papers and in Chap. 13.
2. Neurological Tests for Models of Stroke 2.1. Somatosensory Functions
2.1.1. Sensorimotor Asymmetry (Sticky Dot) Test
A number of somatosensory tests such as feeding and food manipulation can be performed by observation in the home cage. Stroke models often use more formal tests that require removing the animal from its home cage, as outlined below. In stroke patients, simultaneous extinction is a reliable predictor of chronic residual deficits (1). The sticky dot test can be used to determine cutaneous sensitivity and sensorimotor integration in rats and mice (2). This test indicates sensorimotor impairments after unilateral lesions involving the sensorimotor
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