Department of Neurosurgery, University Hospital of Schleswig Holstein Campus Kiel, Kiel, Germany.
Department of Neurosurgery, University Hospital of Schleswig Holstein Campus Kiel, Kiel, Germany; Department of Pediatric Neurosurgery, AsklepiosKlinik Sankt Augustin GmbH, Sankt Augustin, Germany.
World Neurosurg. 2020 Sep;141:e633-e644. doi: 10.1016/j.wneu.2020.05.256. Epub 2020 Jun 6.
Lumbosacral lipomas (LSLs), one form of closed spinal dysraphism, are congenital disorders of the terminal spinal cord (SC). Delayed neurologic deterioration often occurs in the subsequent developmental course of the patient. Identifying the cellular and molecular factors underlying the progressive damage to neural structures is a prerequisite for developing treatment strategies for LSLs.
Nine LSL specimens obtained from the SC/lipoma interface during surgical resection were examined. Normal SC tissue served as a control. Clinical characteristics were obtained, and spinal magnetic resonance imaging was re-evaluated. Cellular marker profiles were established. Immunoreactivity (IR) of hypoxia-inducible factor 1α (HIF-1α/-2α), erythropoietin (Epo)/erythropoietin receptor (EpoR), interleukin-1β (IL-1β)/IL-1R1, and tumor necrosis factor α/tumor necrosis factor receptor type 1 were analyzed qualitatively and semiquantitatively by densitometry. Colabeling with cellular markers was determined by multifluorescence labeling. Cytokines were further analyzed by real-time reverse transcription polymerase chain reaction.
LSL specimens showed significant gliosis. HIF-1α/HIF-2α-IR and Epo/Epo-IR were found at significantly higher levels in the LSL specimens, as were IL-1β-/IL-1β receptor type 1 (IL1-R1) and tumor necrosis factor α/tumor necrosis factor receptor type 1 (P < 0.001), than were the controls. At the messenger RNA level, cytokines appeared partially induced. Double immunofluorescence labeling confirmed the costaining of these factors with inflammatory and glial markers.
The expression of hypoxia-related and inflammatory mediators was shown for the first time in LSL specimens. These factors might play a role in multifactorial secondary lesion cascades underlying further damage to the neural placode in closed dysraphism.
腰骶部脂肪瘤（LSL）是闭合性脊髓脊膜膨出的一种形式，是终丝脊髓（SC）的先天性疾病。患者在随后的发育过程中，神经功能常常会逐渐恶化。确定导致神经结构进行性损伤的细胞和分子因素是为 LSL 开发治疗策略的前提。
在手术切除时，从 SC/脂肪瘤交界处获得了 9 个 LSL 标本，并以正常 SC 组织作为对照。获得了临床特征，并重新评估了脊髓磁共振成像。建立了细胞标志物图谱。通过密度测定法，对缺氧诱导因子 1α（HIF-1α/-2α）、促红细胞生成素（Epo）/促红细胞生成素受体（EpoR）、白细胞介素-1β（IL-1β）/白细胞介素-1R1 和肿瘤坏死因子 α/肿瘤坏死因子受体 1 的免疫反应性（IR）进行了定性和半定量分析。通过多荧光标记确定细胞标志物的共标记。通过实时逆转录聚合酶链反应进一步分析细胞因子。
LSL 标本显示明显的神经胶质增生。与对照组相比，LSL 标本中 HIF-1α/HIF-2α-IR 和 Epo/Epo-IR 的水平明显升高（P <0.001），IL-1β/IL-1β 受体 1（IL1-R1）和肿瘤坏死因子 α/肿瘤坏死因子受体 1（TNF-α/TNF-R1）也是如此。在信使 RNA 水平上，细胞因子似乎部分被诱导。双重免疫荧光标记证实了这些因子与炎症和神经胶质标志物的共染色。
首次在 LSL 标本中显示出与缺氧相关和炎症介质的表达。这些因素可能在闭合性脊膜膨出中神经嵴的多因素继发性损伤级联反应中发挥作用。
