INTRODUCTION Unfortunately, over 40% of stroke victims have pre-existing diabetes which not only increases their risk of stroke up to 2-6 fold, but also worsens both functional recovery and the severity of cognitive impairment. Our lab has recently linked the chronic inflammation in diabetes to poor functional outcomes and exacerbated cognitive impairment, also known as post-stroke cognitive impairment (PSCI). Although we have shown that the development of PSCI in diabetes is associated with the upregulation and the activation of pro-inflammatory microglia, we have not established direct causation between the two. To this end, we evaluated the role of microglia in the development of PSCI. METHODS At 13 weeks of age, diabetic animals received bilateral intracerebroventricular (ICV) injections of short hairpin RNA (shRNA) lentiviral particles targeting the colony stimulating factor 1 receptor (CSF1R). After 14 days, animals were subjected to 60 min middle cerebral artery occlusion (MCAO) or sham surgery. Adhesive removal task (ART), novel object recognition (NOR), and 2-trial Y-maze were utilized to evaluate sensorimotor and cognitive function. Tissue from freshly harvested brains was analyzed by flow cytometry and immunohistochemistry. RESULTS CSF1R silencing resulted in a 94% knockdown of residential microglia to relieve inflammation and improve myelination of white matter in the brain. This prevented cognitive decline in diabetic animals. CONCLUSION Microglial activation after stroke in diabetes may be causally related to the development of delayed neurodegeneration and PSCI.

中文翻译：

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小胶质细胞敲低可减少实验性中风后糖尿病动物的炎症并保留认知能力。


简介 不幸的是，超过 40% 的中风患者既往患有糖尿病，这不仅使他们中风的风险增加 2-6 倍，而且还会恶化功能恢复和认知障碍的严重程度。我们的实验室最近将糖尿病的慢性炎症与功能不良和认知障碍加剧（也称为中风后认知障碍（PSCI））联系起来。尽管我们已经证明糖尿病中 PSCI 的发生与促炎性小胶质细胞的上调和激活有关，但我们尚未确定两者之间的直接因果关系。为此，我们评估了小胶质细胞在 PSCI 发展中的作用。方法 在 13 周龄时，糖尿病动物接受双侧脑室内 (ICV) 注射靶向集落刺激因子 1 受体 (CSF1R) 的短发夹 RNA (shRNA) 慢病毒颗粒。 14天后，对动物进行60分钟大脑中动脉闭塞（MCAO）或假手术。利用粘合剂去除任务（ART）、新物体识别（NOR）和二试验Y迷宫来评估感觉运动和认知功能。通过流式细胞术和免疫组织化学分析新鲜采集的大脑组织。结果 CSF1R 沉默导致驻留小胶质细胞减少 94%，从而缓解炎症并改善大脑白质的髓鞘形成。这可以防止糖尿病动物的认知能力下降。结论 糖尿病患者中风后小胶质细胞的激活可能与迟发性神经变性和 PSCI 的发生有关。