Kalantari Aref, Hambrock Carolin, Grefkes Christian, Fink Gereon R, Aswendt Markus
University of Cologne, Faculty of Medicine and University Hospital Cologne, Department of Neurology, Cologne, Germany.
Goethe University Frankfurt, University Hospital, Department of Neurology, Frankfurt am Main, Germany.
Exp Neurol. 2025 Apr;386:115180. doi: 10.1016/j.expneurol.2025.115180. Epub 2025 Feb 4.
The proportional Recovery Rule (PRR) has been frequently used to predict recovery of lost motor function in acute stroke patients. However, it still needs to be explored whether the same concept applies to preclinical, i.e. animal models of stroke recovery. To address this question, we investigated behavioral data from 125 adult male C57Bl/6 J mice with photothrombotic strokes in the sensorimotor cortex. Lesion size and location were determined in the first week using in vivo T2-weighted MRI. Motor recovery was evaluated repeatedly over four weeks using the cylinder, grid walk, and rotating beam test. Recovery trajectories were analyzed using a newly formulated Mouse Recovery Rule (MRR), comparing it against the traditional PRR. Initial findings indicated variable recovery patterns, which were separated using a stepwise linear regression approach resulting in two clusters: 47 % PRR and 53 % MRR. No significant correlation was found between recovery patterns and lesion size or location, suggesting that other biological factors drive individual differences in recovery. Of note, in the MRR cluster, animals recovered to 90 % of their initial behavioral state within the first four weeks post-stroke, which is higher than the 70 % recovery usually reported in human PRR studies. This study demonstrates the complexity of translating the PRR to stroke recovery models in mice and underscores the need for species-specific recovery models. Our findings have implications for designing and interpreting therapeutic strategies for stroke recovery in preclinical settings, with the potential to improve the predictive accuracy of stroke recovery assessments.
比例恢复规则（PRR）经常被用于预测急性中风患者运动功能丧失后的恢复情况。然而，同样的概念是否适用于临床前研究，即中风恢复的动物模型，仍有待探索。为了解决这个问题，我们调查了125只成年雄性C57Bl/6 J小鼠在感觉运动皮层发生光血栓性中风后的行为数据。在第一周使用体内T2加权MRI确定损伤大小和位置。在四周内使用圆柱体、网格行走和旋转光束测试反复评估运动恢复情况。使用新制定的小鼠恢复规则（MRR）分析恢复轨迹，并将其与传统的PRR进行比较。初步结果表明存在不同的恢复模式，使用逐步线性回归方法将其分开，结果形成两个集群：47%符合PRR，53%符合MRR。在恢复模式与损伤大小或位置之间未发现显著相关性，这表明其他生物学因素驱动了恢复中的个体差异。值得注意的是，在符合MRR的集群中，动物在中风后的前四周内恢复到其初始行为状态的90%，这高于人类PRR研究中通常报道的70%的恢复率。这项研究证明了将PRR转化为小鼠中风恢复模型的复杂性，并强调了需要物种特异性恢复模型。我们的研究结果对临床前环境中中风恢复治疗策略的设计和解释具有启示意义，有可能提高中风恢复评估的预测准确性。
