Type 2 diabetes (T2D) hampers recovery after stroke, but the underling mechanisms are mostly unknown. In a recently published study (Pintana et al. in Clin Sci (Lond) 133(13):1367-1386, 2019), we showed that impaired recovery in T2D was associated with persistent atrophy of parvalbumin+ interneurons in the damaged striatum. In the current work, which is an extension of the abovementioned study, we investigated whether somatostatin (SOM)+ interneurons are also affected by T2D during the stroke recovery phase. C57Bl/6j mice were fed with high-fat diet or standard diet (SD) for 12 months and subjected to 30-min transient middle cerebral artery occlusion (tMCAO). SOM+ cell number/density in the striatum was assessed by immunohistochemistry 2 and 6 weeks after tMCAO in peri-infarct and infarct areas. This was possible by establishing a computer-based quantification method that compensates the post-stroke tissue deformation and the irregular cell distribution. SOM+ interneurons largely survived the stroke as seen at 2 weeks. Remarkably, 6 weeks after stroke, the number of SOM+ interneurons increased (vs. contralateral striatum) in SD-fed mice in both peri-infarct and infarct areas. However, this increase did not result from neurogenesis. T2D completely abolished this effect specifically in the in the infarct area. The results suggest that the up-regulation of SOM expression in the post-stroke phase could be related to neurological recovery and T2D could inhibit this process. We also present a new and precise method for cell counting in the stroke-damaged striatum that allows to reveal accurate, area-related effects of stroke on cell number.

中文翻译：

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糖尿病抑制中风引起的生长抑素表达神经元的增加：中风恢复受损的潜在机制。


2 型糖尿病 (T2D) 会阻碍中风后的恢复，但其基本机制大多未知。在最近发表的一项研究中（Pintana 等人，发表于 Clin Sci (Lond) 133(13):1367-1386, 2019），我们发现 T2D 恢复受损与受损纹状体中小清蛋白+中间神经元的持续萎缩有关。目前的工作是上述研究的延伸，我们研究了生长抑素 (SOM)+ 中间神经元在中风恢复阶段是否也受到 T2D 的影响。 C57Bl/6j 小鼠用高脂肪饮食或标准饮食 (SD) 喂养 12 个月，并进行 30 分钟短暂大脑中动脉闭塞 (tMCAO)。 tMCAO 后 2 周和 6 周通过免疫组织化学评估梗塞周围和梗塞区域纹状体中的 SOM+ 细胞数量/密度。这是通过建立基于计算机的量化方法来补偿中风后组织变形和不规则细胞分布而实现的。从 2 周时可见，SOM+ 中间神经元大部分在中风中幸存下来。值得注意的是，中风后 6 周，SD 喂养的小鼠在梗塞周围和梗塞区域的 SOM+ 中间神经元数量（相对于对侧纹状体）均有所增加。然而，这种增加并不是由神经发生引起的。 T2D 完全消除了这种效应，特别是在梗塞区域。结果表明，中风后阶段SOM表达上调可能与神经功能恢复有关，而T2D可以抑制这一过程。我们还提出了一种新的、精确的中风受损纹状体细胞计数方法，可以准确地揭示中风对细胞数量的区域相关影响。