Jakovcevski Igor, Acar Ayse, Schwindenhammer Benjamin, Hamad Mohammad I K, Reiss Gebhard, Förster Eckart, Schachner Melitta
Institut für Anatomie und Klinische Morphologie, Universität Witten/Herdecke, 58455 Witten, Germany.
Department of Neuroanatomy and Molecular Brain Research, Institute of Anatomy, Ruhr-Universität Bochum, 44780 Bochum, Germany.
Biomolecules. 2025 Aug 28;15(9):1247. doi: 10.3390/biom15091247.
After spinal cord injury, pathological changes predominantly proceed caudal to the site of injury. To what extent these changes contribute to abnormalities during regeneration is poorly understood. Here, we addressed this question with a low-thoracic compression injury mouse model. The total numbers of immunohistochemically stained neuronal and glial cell types in the lumbar spinal cord were stereologically determined 6 weeks after injury. We also investigated injured mice deficient in close homolog of L1 (CHL1), which had been reported to recover better after injury than their wild-type littermates. We here report that there were no differences between genotypes in uninjured animals. In both injured CHL1-deficient and wild-type littermates, gray and white matter volumes were decreased as compared with uninjured mice. Numbers of motoneurons and parvalbumin-expressing interneurons were also reduced in both genotypes. Numbers of interneurons in injured mutant mice were lower than in wild-type littermates. Whereas injury did not affect numbers of astrocytes and oligodendrocytes in the gray matter, numbers of microglia/macrophages were increased. In the mutant white matter, numbers of oligodendrocytes were reduced, with no changes in numbers of astrocytes and microglia. A loss of motoneurons and interneurons was observed in both genotypes, but loss of interneurons was more prominent in the absence of CHL1. We propose that, after injury, CHL1 deficiency causes deficits in structural outcome not seen after injury of wild-type mice.
脊髓损伤后，病理变化主要发生在损伤部位的尾端。这些变化在再生过程中对异常情况的影响程度尚不清楚。在此，我们通过低胸段压迫性损伤小鼠模型来解决这个问题。在损伤6周后，通过立体学方法确定腰段脊髓中免疫组化染色的神经元和胶质细胞类型的总数。我们还研究了缺乏L1紧密同源物（CHL1）的损伤小鼠，据报道这些小鼠在损伤后比其野生型同窝小鼠恢复得更好。我们在此报告，未受伤动物的基因型之间没有差异。在受伤的CHL1缺陷型和野生型同窝小鼠中，与未受伤小鼠相比，灰质和白质体积均减少。两种基因型的运动神经元和表达小白蛋白的中间神经元数量也减少。受伤的突变小鼠中的中间神经元数量低于野生型同窝小鼠。虽然损伤不影响灰质中星形胶质细胞和少突胶质细胞的数量，但小胶质细胞/巨噬细胞的数量增加。在突变型白质中，少突胶质细胞数量减少，星形胶质细胞和小胶质细胞数量没有变化。在两种基因型中均观察到运动神经元和中间神经元的丢失，但在缺乏CHL1的情况下，中间神经元的丢失更为明显。我们提出，损伤后，CHL1缺陷会导致野生型小鼠损伤后未见的结构结果缺陷。
