Oklinski M K, Choi H-J, Kwon T-H
Department of Biochemistry and Cell Biology, School of Medicine, Kyungpook National University, Taegu 41944, South Korea.
Department of Biochemistry and Cell Biology, School of Medicine, Kyungpook National University, Taegu 41944, South Korea.
Neuroscience. 2015 Dec 17;311:138-52. doi: 10.1016/j.neuroscience.2015.10.025. Epub 2015 Oct 19.
Aquaporin-4 (AQP4), a water channel protein, is expressed mainly in the perivascular end-feet of astrocytes in the brain and spinal cord. Dysregulation of AQP4 is critically associated with abnormal water transport in the astrocytes. We aimed to examine whether peripheral nerve injury (PNI) could induce the changes of AQP4 expression and astrocytic morphology in the spinal cord. Two different PNI models [partial sciatic nerve transection (PST) and chronic constriction injury (CCI)] were established on the left sciatic nerve in Sprague-Dawley rats, which decreased the pain withdrawal threshold in the ipsilateral hind paws. Both PNI models were associated with a persistent up-regulation of AQP4 in the ipsilateral dorsal horn at the lower lumbar region over 3 weeks, despite an absence of direct injury to the spinal cord. Three-dimensional reconstruction of astrocytes was made and morphometric analysis was done. Up-regulation of AQP4 was accompanied by a significant increase in the length and volume of astrocytic processes and the number of branch points. The most prominent changes were present in the distal processes of the astrocytes and the changes were maintained throughout the whole experimental period. Extravasation of systemically administered tracers Evans Blue and sodium fluorescein was not seen in both models. Taken together, PNI was associated with a long-lasting AQP4 up-regulation and enlargement of astrocytic processes in the spinal cord in rats, both of which were not related to the disruption of blood-spinal cord barrier. The findings could provide novel insights on the understanding of pathophysiology of spinal cords after PNI.
水通道蛋白4（AQP4）是一种水通道蛋白，主要表达于脑和脊髓中星形胶质细胞的血管周围终足。AQP4的失调与星形胶质细胞中异常的水转运密切相关。我们旨在研究周围神经损伤（PNI）是否会诱导脊髓中AQP4表达和星形胶质细胞形态的改变。在Sprague-Dawley大鼠的左侧坐骨神经上建立了两种不同的PNI模型[坐骨神经部分横断（PST）和慢性压迫损伤（CCI）]，这两种模型均降低了同侧后爪的疼痛撤离阈值。尽管脊髓没有受到直接损伤，但在3周多的时间里，两种PNI模型均与下腰段同侧背角中AQP4的持续上调有关。对星形胶质细胞进行了三维重建并进行了形态计量分析。AQP4的上调伴随着星形胶质细胞突起的长度、体积以及分支点数量的显著增加。最显著的变化出现在星形胶质细胞的远端突起中，并且这些变化在整个实验期间都持续存在。在两种模型中均未观察到全身注射示踪剂伊文思蓝和荧光素钠的外渗现象。综上所述，PNI与大鼠脊髓中AQP4的长期上调以及星形胶质细胞突起的增大有关，这两者均与血脊髓屏障的破坏无关。这些发现可能为理解PNI后脊髓的病理生理学提供新的见解。
