Neonatal stroke is a leading cause of long‐term disability and currently available rehabilitation treatments are insufficient to promote recovery. Activating neural precursor cells (NPCs) in adult rodents, in combination with rehabilitation, can accelerate functional recovery following stroke. Here, we describe a novel method of constraint‐induced movement therapy (CIMT) in a rodent model of neonatal stroke that leads to improved functional outcomes, and we asked whether the recovery was correlated with expansion of NPCs. A hypoxia/ischemia (H/I) injury was induced on postnatal day 8 (PND8) via unilateral carotid artery ligation followed by systemic hypoxia. One week and two weeks post‐H/I, CIMT was administered in the form of 3 botulinum toxin (Botox) injections, which induced temporary paralysis in the unaffected limb. Functional recovery was assessed using the foot fault task. NPC proliferation was assessed using the neurosphere assay and EdU immunohistochemistry. We found that neonatal H/I injury alone expands the NPC pool by >2.5‐fold relative to controls. We determined that using Botox injections as a method to provide CIMT results in significant functional motor recovery after H/I. However, CIMT does not lead to enhanced NPC activation or migration into the injured parenchyma in vivo. At the time of functional recovery, increased numbers of proliferating inflammatory cells were found within the injured motor cortex. Together, these findings suggest that NPC activation following CIMT does not account for the observed functional improvement and suggests that CIMT‐mediated modification of the CNS inflammatory response may play a role in the motor recovery.

中文翻译：

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在没有神经前体激活的情况下，约束诱导的运动疗法可促进新生儿中风后的运动恢复

新生儿中风是长期残疾的主要原因，目前可用的康复治疗不足以促进康复。激活成年啮齿动物中的神经前体细胞（NPC），与康复相结合，可以加速中风后的功能恢复。在这里，我们描述了一种在新生儿中风的啮齿动物模型中进行约束诱导运动疗法（CIMT）的新方法，该方法可改善功能结果，并询问其恢复是否与NPC的扩张相关。出生后第8天（PND8）通过单侧颈动脉结扎引起系统性缺氧，从而引起缺氧/缺血（H / I）损伤。在H / I后一周和两周，以3次肉毒杆菌毒素（Botox）注射的形式给予CIMT，这会导致未受影响的肢体暂时瘫痪。使用足部损伤任务评估功能恢复。使用神经球测定法和EdU免疫组织化学评估NPC增殖。我们发现，仅新生儿H / I损伤可使NPC库相对于对照组扩大> 2.5倍。我们确定使用肉毒杆菌注射作为提供CIMT的方法可在H / I后导致明显的功能性运动恢复。但是，CIMT不会导致增强的NPC活化或在体内迁移到受损的薄壁组织中。在功能恢复时，发现受伤的运动皮层内增殖的炎性细胞数量增加。总之，这些发现表明，CIMT后的NPC活化不能解释观察到的功能改善，并且表明CIMT介导的CNS炎症反应的修饰可能在运动恢复中起作用。