Freret Thomas, Schumann-Bard Pascale, Boulouard Michel, Bouet Valentine
GMPc - Groupe Mémoire et Plasticité comportementale, EA4259, Université de Caen Basse-Normandie, Caen, France.
Exp Transl Stroke Med. 2011 Jun 18;3:6. doi: 10.1186/2040-7378-3-6.
Despite extensive research efforts in the field of cerebral ischemia, numerous disappointments came from the translational step. Even if experimental studies showed a large number of promising drugs, most of them failed to be efficient in clinical trials. Based on these reports, factors that play a significant role in causing outcome differences between animal experiments and clinical trials have been identified; and latest works in the field have tried to discard them in order to improve the scope of the results. Nevertheless, efforts must be maintained, especially for long-term functional evaluations. As observed in clinical practice, animals display a large degree of spontaneous recovery after stroke. The neurological impairment, assessed by basic items, typically disappears during the firsts week following stroke in rodents. On the contrary, more demanding sensorimotor and cognitive tasks underline other deficits, which are usually long-lasting. Unfortunately, studies addressing such behavioral impairments are less abundant. Because the characterization of long-term functional recovery is critical for evaluating the efficacy of potential therapeutic agents in experimental strokes, behavioral tests that proved sensitive enough to detect long-term deficits are reported here. And since the ultimate goal of any stroke therapy is the restoration of normal function, an objective appraisal of the behavioral deficits should be done.
尽管在脑缺血领域进行了广泛的研究,但转化阶段却带来了诸多失望。即便实验研究显示出大量有前景的药物,但其中大多数在临床试验中未能取得成效。基于这些报告,已确定了在导致动物实验与临床试验结果差异方面起重要作用的因素;该领域的最新研究试图排除这些因素以扩大研究结果的范围。然而,仍需持续努力,尤其是在长期功能评估方面。正如临床实践中所观察到的,动物在中风后会有很大程度的自发恢复。通过基本指标评估的神经功能缺损,在啮齿动物中风后的第一周通常会消失。相反,更具挑战性的感觉运动和认知任务则凸显出其他通常持续时间较长的缺陷。遗憾的是,针对此类行为损伤的研究较少。由于长期功能恢复的特征对于评估实验性中风中潜在治疗药物的疗效至关重要,本文报告了经证明足够灵敏以检测长期缺陷的行为测试。并且由于任何中风治疗的最终目标都是恢复正常功能,因此应对行为缺陷进行客观评估。