由于中风治疗仍然仅限于少数患者,已经加强了对缺血形成过程中病理生理过程的理解,可能允许开发特定的治疗干预措施。在这种情况下,在向持久组织损伤过渡的过程中,细胞骨架元素作为关键参与者变得明显。这项研究着重于与缺血相关的细胞骨架改变,特别着重于微管相关蛋白和神经丝轻链(NF-L)。将免疫组织化学分析应用于实验性中风后的小鼠和大鼠的脑切片以及来自中风患者的自体样品。要考虑翻译方面,大鼠中风的血栓栓塞模型,密切模仿人类的处境,除了基于细丝的小鼠局灶性脑缺血模型外,还使用了这种方法。缺血发作后一天,在缺血区域,微管相关蛋白tau和微管相关蛋白2(MAP2)的免疫反应性降低。这些发现始终存在于受缺血影响的纹状体和新皮质中。以一种完全相反的方式,缺血区在神经病理学改变的纤维中显示NF-L免疫反应性,局部聚集可能与降解的细胞体和新皮质锥体细胞有关。值得注意的是,在来自人脑样品的梗塞组织中也证实了NF-L的上调。此外,对啮齿动物脑组织的分析显示,在受缺血影响的海马中,开瓶器卷曲样纤维是MAP2的特殊特征。总之,本研究为局灶性脑缺血后微管相关蛋白和神经丝的相反反应提供了证据.因此,细胞骨架元素似乎是中风治疗的有希望的靶标。
As stroke therapies are still limited to a minority of patients, efforts have been intensified to an improved understanding of pathophysiological processes during ischemia formation, potentially allowing the development of specific therapeutic interventions. In this context, cytoskeletal elements became evident as key players during the transition process towards long-lasting tissue damage. This study focused on ischemia-related alterations of the cytoskeleton with a special focus on microtubule-associated proteins and neurofilament light chains (NF-L). Immunohistochemical analyses were applied to brain sections of mice and rats after experimental stroke and to autoptic samples from a stroke patient. To consider translational aspects, a thromboembolic model of stroke in rats, closely mimicking the human situation, was used in addition to the filament-based model of focal cerebral ischemia in mice. One day after ischemia onset, immunoreactivity of microtubule-associated protein tau and microtubule-associated protein-2 (MAP2) was reduced in ischemic areas. These findings were consistently present in the ischemia-affected striatum and the neocortex. In a quite opposite fashion, ischemic areas displayed NF-L-immunoreactivity in neuropathologically altered fibers, local agglomerations probably related to degraded cell bodies and neocortical pyramidal cells. Notably, up-regulation of NF-L was also confirmed in infarcted tissue from a human brain sample. Furthermore, analyses of rodent brain tissue revealed corkscrew curl-like fibers as a special feature of MAP2 in the ischemia-affected hippocampus. In conclusion, this study provides evidence for an opposite reaction of microtubule-associated proteins and neurofilaments after focal cerebral ischemia. Accordingly, cytoskeletal elements appear as a promising target for stroke treatment.