新型非人灵长类内囊梗死模型的运动损害与适应
研究建立一种新型非人灵长类局灶性内囊梗死模型，对3只成年雄性恒河猴左侧内囊后肢注射ET-1，采用自身前后对照设计并结合MRI与组织学确认梗死。梗死后所有动物患侧手使用显著减少，部分动物出现伸腕屈指代偿姿势，提示该模型可复现人类皮质下卒中的远端运动缺陷与个体差异。
要点
- 所有动物梗死后患侧手使用显著减少（Fisher精确检验，均P<0.05）。
- 2只动物中心外任务成功率下降（P<0.01），1只路径长度增加（P=0.0015）。
- 2只动物4周内出现伸腕屈指代偿姿势，纳入模型后拟合显著改善（P<0.0001）。
核心结论
- 该模型复现了人类皮质下卒中的关键特征，包括持续性远端运动缺陷、手偏好改变、系统性运动适应及个体间差异，可作为研究卒中机制和评估促恢复干预的转化平台。
研究设计与样本
- 自身前后对照设计，3只成年雄性恒河猴（Macaca mulatta，5-10岁）左侧内囊后肢立体定向注射ET-1（0.5 µg/µL；总量9-10 µL），以MRI与死后组织学确认梗死。
- 运动功能采用中心外操纵杆任务与Klüver板任务评估，手姿势由盲法评分者额外评分以量化适应。
- 梗死前后比较采用广义线性混合模型并纳入每次会话随机效应，适应协变量采用似然比检验评估。
主要发现
- 所有动物梗死后患侧手使用显著减少（Fisher精确检验；均P<0.05）。
- 广义线性混合模型显示2只动物中心外成功率下降（P<0.01），1只路径长度增加（P=0.0015）。
- 汇总广义线性混合模型显示梗死后取回时间（估计值=0.73 s；P<0.0001）与手指屈曲（估计值=0.727；P<0.0001）显著增加。
- 2只动物在4周内出现伸腕屈指代偿姿势；将该姿势特征加入广义线性混合模型后拟合显著改善（似然比检验；P<0.0001）。
临床怎么用
- 该模型可作为转化平台，用于研究皮质下卒中运动损害的机制并评估促恢复干预，但尚未提供临床治疗推荐。
局限性
- 探索性研究仅纳入3只动物，梗死体积存在变异，结果需更大样本验证。
以上解读依据论文摘要（全文未开放获取或许可不允许翻译转载）。
原文
BACKGROUND: Loss of hand control is a major source of poststroke disability, particularly when infarcts involve subcortical white matter. Yet, most preclinical models target the cortex and infer recovery from task performance without quantifying whether improvements reflect restoration or adaptation. To address this, we developed a novel nonhuman primate model of focal internal capsule infarct. This study is exploratory and hypothesis-testing, including prespecified hypotheses regarding motor impairment and adaptation. METHODS: Three adult male rhesus macaques (Macaca mulatta, 5-10 years) received stereotactically guided ET-1 (endothelin-1) injections (0.5 µg/µL; 9-10 µL total) into the left posterior limb of the internal capsule in a within-subject pre-infarct versus post-infarct design. Infarcts were characterized by magnetic resonance imaging and postmortem histology. Motor function was tested with a center-out joystick task and a Klüver board task using standard behavioral metrics; hand posture was additionally scored by blinded raters to quantify adaptation. Pre-infarct versus post-infarct comparisons used generalized linear mixed models with per-session random effects; adaptation covariates were evaluated using likelihood-ratio tests. RESULTS: Magnetic resonance imaging and histology confirmed focal infarcts centered on the posterior limb of the internal capsule, with variable volumes. All animals significantly reduced contralesional hand use post-infarct (Fisher exact test; all P<0.05). Generalized linear mixed models showed reduced center-out success rates in 2 animals (P<0.01) and increased path length in one (P=0.0015). Pooled generalized linear mixed models showed significant post-infarct increases in retrieval time (estimate=0.73 s; P<0.0001) and digit flexions (estimate=0.727; P<0.0001). Two animals developed a compensatory wrist-extended, digit-flexed posture by 4 weeks; augmenting generalized linear mixed models with these postural features significantly improved fit (likelihood-ratio tests; P<0.0001). CONCLUSIONS: This model recapitulates key features of human subcortical stroke, including persistent distal motor deficits, shifts in hand preference, systematic motor adaptation, and interindividual variability, establishing a translationally oriented platform for studying stroke mechanisms and evaluating recovery-promoting interventions.
引用
- Sivakumar SS, Anand SA, Brawer L, et al. Motor Impairment and Adaptation in a Novel Nonhuman Primate Model of Internal Capsule Infarct. Stroke. 2026. PMID: 42017256. doi:10.1161/STROKEAHA.125.054365
供执业医师工作参考，不替代临床判断；数值与分级以指南原文为准。