Miyamoto K, Heimann A, Kempski O
Department of Neurosurgery, Nara Medical University, Japan.
J Clin Neurosci. 2001 May;8 Suppl 1:97-105. doi: 10.1054/jocn.2001.0887.
The pathophysiology of sinus vein thrombosis (SVT) is still controversial in patients and experimental animals, the microcirculatory alterations in particular. This study was designed to develop a new sinus vein thrombosis model and to further elucidate pathophysiological events such as the relationship between local and regional cerebral blood flow and haemoglobin oxygen saturation (HbSO2), changes of the microvasculature, leukocyte behaviour and brain tissue damage.
In a first experimental series, animals were divided into two groups which resulted from different procedures of inducing SVT. In the SSS middle occlusion group (SMO group), SVT was induced by the ligation of the superior sagittal sinus right in the middle between the bregma and the confluence sinum. In the SSS posterior occlusion group (SPO group) the ligation was performed close to the confluence sinum. Regional cerebral blood flow (rCBF) was assessed at 36 identical locations by laser Doppler flowmetry together with regional haemoglobin oxygen saturation (HbSO2). In a second series of experiments SVT was induced by ligation of the SSS close to the confluence sinum (SVT group) to study effects on the cortical microcirculation. A sham operation was performed in six animals (sham group). In both groups, an intravital microscopic double tracing technique was utilised for evaluating microvessel structures and leukocyte behaviour. The images were recorded on videotape for evaluating alterations of microvessel (venules, arterioles and capillaries) diameters and numbers of leukocyte rollers and stickers by a digital video analyser. Animals were sacrificed for histological evaluation after 5 days.
The posterior sinus ligation caused a significant decrease of rCBF and HbSO2 and brain tissue damage which was not seen in the SMO group. Alteration of rCBF and HbSO2 were positively correlated with infarct size in the SPO group only, where venous infarction was easily reproduced. Therefore, it is suggested that this model is suitable for studying SVT in Mongolian gerbils. Intravital microscopy of the cortical microcirculation revealed no significant changes of vessels diameter in the sham group, whereas a significant dilation of veins and capillaries was seen in the SVT group. Numbers of leukocyte rollers and stickers were positively correlated with infarct size.
Microcirculatory alterations and brain tissue damage from SVT in the Mongolian gerbil depend on the SSS occlusion site. The newly established mongolian gerbil sinus-vein thrombosis model has advantages compared to previously reported sinus-vein thrombosis models such as easy handling, easy technique, highly reproducibility, and good observation of microcirculatory event. The model allows for studies of cerebral low-flow conditions such as expected to occur in an ischaemic penumbra zone.
在患者和实验动物中,静脉窦血栓形成(SVT)的病理生理学仍存在争议,尤其是微循环改变方面。本研究旨在建立一种新的静脉窦血栓形成模型,并进一步阐明病理生理事件,如局部和区域脑血流量与血红蛋白氧饱和度(HbSO2)之间的关系、微血管变化、白细胞行为和脑组织损伤。
在第一个实验系列中,动物被分为两组,这两组是通过不同的诱导SVT的方法产生的。在矢状窦中部闭塞组(SMO组),通过在囟门与窦汇之间的中部结扎上矢状窦来诱导SVT。在矢状窦后部闭塞组(SPO组),结扎靠近窦汇处。通过激光多普勒血流仪在36个相同位置评估区域脑血流量(rCBF)以及区域血红蛋白氧饱和度(HbSO2)。在第二个实验系列中,通过在靠近窦汇处结扎上矢状窦诱导SVT(SVT组)以研究对皮质微循环的影响。对6只动物进行假手术(假手术组)。在两组中,均利用活体显微镜双示踪技术评估微血管结构和白细胞行为。图像被记录在录像带上,以便通过数字视频分析仪评估微血管(小静脉、小动脉和毛细血管)直径的改变以及白细胞滚动和黏附的数量。5天后处死动物进行组织学评估。
后部窦结扎导致rCBF和HbSO2显著降低以及脑组织损伤,而SMO组未出现这种情况。仅在容易重现静脉梗死的SPO组中,rCBF和HbSO2的改变与梗死灶大小呈正相关。因此,提示该模型适用于研究蒙古沙鼠的SVT。皮质微循环的活体显微镜检查显示假手术组血管直径无显著变化,而SVT组可见静脉和毛细血管显著扩张。白细胞滚动和黏附的数量与梗死灶大小呈正相关。
蒙古沙鼠中SVT引起的微循环改变和脑组织损伤取决于上矢状窦闭塞部位。新建立的蒙古沙鼠静脉窦血栓形成模型与先前报道的静脉窦血栓形成模型相比具有优势,如操作简便、技术简单、高度可重复性以及对微循环事件的良好观察。该模型可用于研究脑低流量状态,如预期在缺血半暗带中发生的情况。