Institute of Biochemistry and Cell Biology, Medical Faculty, University of Magdeburg, Leipziger Strasse 44, 39120, Magdeburg, Germany.
Department of Anesthesiology, Medical Faculty, University of Magdeburg, Magdeburg, Germany.
Neurocrit Care. 2021 Jun;34(3):844-855. doi: 10.1007/s12028-020-01094-z. Epub 2020 Sep 23.
After cardiac arrest/resuscitation (CA/R), animals often had massive functional restrictions including spastic paralysis of hind legs, disturbed balance and reflex abnormalities. Patients who have survived CA also develop movement restrictions/disorders. A successful therapy requires detailed knowledge of the intrinsic damage pattern and the respective mechanisms. Beside neurodegenerations in the cerebellum and cortex, neuronal loss in the spinal cord could be a further origin of such movement artifacts.
Thus, we aimed to evaluate the CA/R-induced degeneration pattern of the lumbar medulla spinalis by immunocytochemical expression of SMI 311 (marker of neuronal perikarya and dendrites), IBA1 (microglia marker), GFAP (marker of astroglia), calbindin D28k (marker of the cellular neuroprotective calcium-buffering system), MnSOD (neuroprotective antioxidant), the transcription factor PPARγ and the mitochondrial marker protein PDH after survival times of 7 and 21 days. The CA/R specimens were compared with those from sham-operated and completely naïve rats. RESULTS & CONCLUSION: The main ACA/R-mediated results were: (1) degeneration of lumbar spinal cord motor neurons, characterized by neuronal pyknotization and peri-neuronal tissue artifacts; (2) attendant activation of microglia in the short-term group; (3) attendant activation of astroglia in the long-term group; (4) degenerative pattern in the intermediate gray matter; (5) activation of the endogenous anti-oxidative defense systems calbindin D28k and MnSOD; (6) activation of the transcription factor PPARγ, especially in glial cells of the gray matter penumbra; and (7) activation of mitochondria. Moreover, marginal signs of anesthesia-induced cell stress were already evident in sham animals when compared with completely naïve spinal cords. A correlation between the NDS and the motor neuronal loss could not be verified. Thus, the NDS appears to be unsuitable as prognostic tool.
心脏骤停/复苏（CA/R）后，动物通常会出现严重的功能受限，包括后腿痉挛性瘫痪、平衡障碍和反射异常。CA 存活的患者也会出现运动受限/障碍。成功的治疗需要详细了解内在损伤模式和各自的机制。除了小脑和皮质中的神经退行性变外，脊髓中的神经元丢失也可能是此类运动障碍的进一步来源。
因此，我们旨在通过免疫细胞化学表达 SMI 311（神经元胞体和树突标志物）、IBA1（小胶质细胞标志物）、GFAP（星形胶质细胞标志物）、钙结合蛋白 D28k（细胞神经保护钙缓冲系统标志物）、MnSOD（神经保护抗氧化剂）、转录因子 PPARγ 和线粒体标志物 PDH，评估 CA/R 诱导的腰髓退变模式。将 CA/R 标本与假手术和完全未处理的大鼠标本进行比较。
主要的 ACA/R 介导结果包括：（1）腰髓运动神经元变性，表现为神经元固缩和周围组织结构破坏；（2）短期组小胶质细胞激活；（3）长期组星形胶质细胞激活；（4）中间灰质退行性变；（5）内源性抗氧化防御系统钙结合蛋白 D28k 和 MnSOD 的激活；（6）转录因子 PPARγ 的激活，特别是在灰质半影区的胶质细胞中；（7）线粒体的激活。此外，与完全未处理的脊髓相比，在假手术动物中已经可以看到麻醉诱导的细胞应激的边缘迹象。NDS 与运动神经元丢失之间没有相关性。因此，NDS 似乎不适合作为预后工具。
