Department of Experimental Medical Science, Lund University, Sölvegatan 17, BMC A1304, 223 62, Lund, SE, Sweden.
Wallenberg Centre for Molecular Medicine, Lund University, Lund, Sweden.
BMC Vet Res. 2021 Jul 20;17(1):250. doi: 10.1186/s12917-021-02954-2.
We report the effects of the presentation of an idiopathic subdural hematoma (SDH) in an adult domestic pig on the glymphatic system, a brain-wide solute clearance system. This accidental finding is based on our recently published study that described this system for the first time in large mammals. Our current results define the need to investigate cerebrovascular pathologies that could compromise glymphatic function in gyrencephalic animal models as a tool to bridge rodent and human glymphatic studies.
The pig underwent intracisternal infusion of a fluorescent tracer under general anesthesia to delineate cerebrospinal fluid (CSF) pathways, and was euthanized at the end of 3 h of tracer circulation. During brain isolation, a hematoma measuring approximately 15 × 35 mm in size beneath the dura was evident overlying fronto-parietal brain surface. Interestingly, CSF tracer distribution was markedly reduced on dorsal, lateral and ventral surfaces of the brain when compared with a control pig that was infused with the same tracer. Furthermore, regional distribution of tracer along the interhemispheric fissure, lateral fissure and hippocampus was 4-5-fold reduced in comparison with a control pig. Microscopically, glial-fibrillary acidic protein and aquaporin-4 water channel immunoreactivities were altered in the SDH pig brain.
This is the first case of impaired glymphatic pathway due to an idiopathic SDH in a pig. Potential etiology could involve an acceleration-deceleration injury inflicted prior to arrival at our housing facility (e.g., during animal transportation) leading to disruption of bridging veins along the superior sagittal sinus and impairing CSF pathways in the whole brain. This accidental finding of globally impaired glymphatic function sheds light on a novel consequence of SDH, which may play a role in the enhanced cognitive decline seen in elderly presenting with chronic SDH.
我们报告了一例成人猪特发性硬脑膜下血肿(SDH)对其脑内液系统(一种广泛的溶质清除系统)的影响。这一意外发现基于我们最近发表的研究,该研究首次在大型哺乳动物中描述了这一系统。我们目前的结果表明,需要研究可能影响脑回动物模型中糖质清除功能的脑血管病变,作为在啮齿动物和人类糖质研究之间架起桥梁的工具。
猪在全身麻醉下接受了脑室内荧光示踪剂输注,以描绘脑脊液(CSF)通路,并在示踪剂循环 3 小时后被安乐死。在脑分离过程中,硬脑膜下可见约 15×35mm 大小的血肿,覆盖额顶叶脑表面。有趣的是,与接受相同示踪剂输注的对照猪相比,脑的背侧、外侧和腹侧表面的 CSF 示踪剂分布明显减少。此外,与对照猪相比,示踪剂沿大脑半球间裂、外侧裂和海马的分布减少了 4-5 倍。显微镜下,SDH 猪脑的胶质纤维酸性蛋白和水通道蛋白-4 的免疫反应性发生改变。
这是首例由于特发性 SDH 导致猪糖质清除途径受损的病例。潜在的病因可能涉及到达我们的饲养设施之前(例如,在动物运输过程中)遭受的加速-减速损伤,导致沿上矢状窦的桥静脉破裂,并损害整个大脑的 CSF 通路。这种意外发现的整体糖质清除功能受损,揭示了 SDH 的一种新后果,这可能在患有慢性 SDH 的老年患者认知能力下降增强中发挥作用。