Behavioral Testing in Mouse Models of Stroke
For decades, histological assessments were the only end-point in stroke research, typically using lesion size determination to evaluate the potential therapeutic effectiveness of an agent in in vivo stroke models. While this approach is indeed valid, fail
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Introduction Stroke is a major health problem and a cause of long-term disability, which puts a heavy burden not only on the patients themselves, but also on their families and on health care systems. This has led generations of scientists to focus their attention on stroke and its pathophysiology in order to develop effective therapies. Unfortunately, years of research, countless studies, and dozens of clinical trials that used potential therapeutic agents validated by carefully planned and evaluated experimental research did not really widen the scope for improvements at the bed-side (see Chap. 1). Recently, this has triggered a growing awareness in the scientific community that a thorough re-examination of the models and techniques used in stroke research is not only necessary, but Ulrich Dirnagl (ed.), Rodent Models of Stroke, Neuromethods, vol. 47, DOI 10.1007/978-1-60761-750-1_13, © Springer Science+Business Media, LLC 2010
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also imperative. According to this new approach, one of the keys to overcome the so-called translational road block is to use behavior testing to assess the functional outcome as a relevant endpoint (1). For decades, histological assessments were the only end point in stroke research, typically using lesion size determination to evaluate the potential therapeutic effectiveness of an agent in in vivo stroke models (see Chap. 15). Lesion sizes are evaluated poststroke after varying survival times that range from hours to weeks, and any significant reduction of the lesion size in the treatment group is considered as the evidence of the beneficial effect of the respective substance or intervention. While this approach is indeed valid, failures in developing effective drugs point out the fact that histological means are simply not enough to evaluate the potential of a drug or intervention and that an evaluation at the functional level is necessary. One also has to keep in mind that the ultimate aim of stroke treatment is to improve the physical health of patients and any drug or intervention must not only protect the brain tissue or promote recovery, but has to also restore function at all levels. The growing appreciation of this situation has led stroke researchers to employ behavioral testing more frequently in their research, making it an important aspect of stroke research (2). Behavior testing is also highly relevant to poststroke emotional and cognitive disturbances. A variety of emotional disturbances including depression, mania, bipolar disorder (very rarely), anxiety disorder and apathy are observed in stroke patients (3). These disturbances not only affect the overall wellbeing of the patient, but also confound the recovery process, so modeling poststroke emotional disturbances and emotional testing draws considerable attention. Cognitive deficits that decrease the quality of life of stroke survivors are also frequently observed after stroke (4, 5). Stroke researchers who aim at exploring poststroke cognitive deficits in animal models must inevitably use
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