Stroke-induced cognitive impairments are of significant concern, however mechanisms that underpin these impairments remain poorly understood and researched. To further characterise cognitive impairments in our frontal cortex stroke model, and to align our assessments with what is used clinically, we tested young C57BL/6J mice trained in operant touchscreen chambers to complete the trial-unique nonmatched-to-location (TUNL) task. Based on baseline performance, animals were given either stroke (n = 12) or sham (n = 12) surgery using a photothrombosis model, bilaterally targeting the frontal cortex. Upon recovery, post-stroke spatial working memory was assessed by varying the degree of separation and delay within TUNL trials. Seven weeks after surgery, animals received a prelimbic injection of the retrograde tracer cholera toxin B (CTB) to access thalamo-PFC connectivity. Tissue was then processed histologically and immunohistochemically to assess infarct volume, astrogliosis and thalamocortical connectivity. Assessment of TUNL probes revealed sensitivity to a frontal cortex stroke (separation: p = 0.0003, delay: p < 0.0001), with stroke animals taking significantly longer (p = 0.0170) during reacquisition of the TUNL task, relative to shams. CTB-positive cell counts revealed a stroke-induced loss of thalamo-PFC connectivity. In addition, quantification of reactive astrogliosis revealed a positive correlation between the degree of astrogliosis expanding into white matter tracts and the development of cognitive impairments. This study reveals a stroke-induced impairment in mice completing the TUNL task. Our findings also demonstrate a significant loss of thalamo-PFC connections and a correlation between white matter reactive astrogliosis and cognitive impairment. Future experiments will investigate therapeutic interventions in the hope of promoting functional improvement in cognition.

中风引起的认知障碍是一个重要的问题，但是支持这些障碍的机制仍然知之甚少和研究。为了进一步表征我们的额叶皮层中风模型中的认知障碍，并使我们的评估与临床使用的结果保持一致，我们测试了在操作性触摸屏室中训练的年轻 C57BL/6J 小鼠，以完成试验独特的非匹配定位 (TUNL) 任务. 根据基线表现，使用光血栓形成模型对动物进行中风（n = 12）或假手术（n = 12），双侧靶向额叶皮层。恢复后，通过改变 TUNL 试验中的分离和延迟程度来评估中风后空间工作记忆。手术后七周，动物接受了逆行示踪霍乱毒素 B (CTB) 的前缘注射以访问丘脑-PFC 连接。然后对组织进行组织学和免疫组织化学处理，以评估梗死体积、星形胶质细胞增生和丘脑皮质连接。TUNL 探针的评估显示对额叶皮层中风的敏感性（分离：p = 0.0003，延迟：p < 0.0001），中风动物花费的时间明显更长（p  = 0.0170) 在重新获取 TUNL 任务期间，相对于 shams。CTB 阳性细胞计数显示中风引起的丘脑-PFC 连接性丧失。此外，反应性星形胶质细胞增生的量化揭示了星形胶质细胞增生扩展到白质束的程度与认知障碍的发展之间的正相关。这项研究揭示了完成 TUNL 任务的小鼠中风引起的损伤。我们的研究结果还证明了丘脑-PFC 连接的显着丧失以及白质反应性星形胶质细胞增生与认知障碍之间的相关性。未来的实验将研究治疗干预，以期促进认知功能的改善。