Animal data

Abstract: From an early age, musicians learn complex motor and auditory skills (e.g., the translation of visually perceived musical symbols into motor commands with simultaneous auditory monitoring of output), which they practice extensively from childhood throughout their entire careers. Using a voxel-by-voxel morphometric technique, we found gray matter volume differences in motor, auditory, and visual-spatial brain regions when comparing professional musicians (keyboard players) with a matched group of amateur musicians and non-musicians. Although some of these multiregional differences could be attributable to innate predisposition, we believe they may represent structural adaptations in response to long-term skill acquisition and the repetitive rehearsal of those skills. This hypothesis is supported by the strong association we found between structural differences, musician status, and practice intensity, as well as the wealth of supporting animal data showing structural changes in response to long-term motor training. However, only future experiments can determine the relative contribution of predisposition and practice.

Abstract: Objective: Preclinical evaluation of neuroprotectants fostered high expectations of clinical efficacy. When not matched, the question arises whether experiments are poor indicators of clinical outcome or whether the best drugs were not taken forward to clinical trial. Therefore, we endeavored to contrast experimental efficacy and scope of testing of drugs used clinically and those tested only experimentally. Methods: We identified neuroprotectants and reports of experimental efficacy via a systematic search. Controlled in vivo and in vitro experiments using functional or histological end points were selected for analysis. Relationships between outcome, drug mechanism, scope of testing, and clinical trial status were assessed statistically. Results: There was no evidence that drugs used clinically (114 drugs) were more effective experimentally than those tested only in animal models (912 drugs), for example, improvement in focal models averaged 31.3 16.7% versus 24.4 32.9%, p > 0.05, respectively. Scope of testing using Stroke Therapy Academic Industry Roundtable (STAIR) criteria was highly variable, and no relationship was found between mechanism and efficacy. Interpretation: The results question whether the most efficacious drugs are being selected for stroke clinical trials. This may partially explain the slow progress in developing treatments. Greater rigor in the conduct, reporting, and analysis of animal data will improve the transition of scientific advances from bench to bedside. Ann Neurol 2006;59:467– 477 A common perception of neuroprotection research is that everything works in animals but nothing works in people. This perception has been reinforced again and again by reports of unsuccessful or mixed outcomes in trials of candidate neuroprotectants in acute stroke patients. If animal experiments are indeed unable to inform clinical decision making, then serious doubts are raised about the utility of animal models of stroke and about the ethics of continuing current animal experimentation practices. 1 In response to this challenge, several excellent reviews and commentaries have tackled the issue of the apparent failure to translate neuroprotection successes from the laboratory to the clinical setting (for examples, see previously published studies 2–7 ). Such com