Szmydynger-Chodobska Joanna, Chung Insung, Koźniewska Ewa, Tran Bao, Harrington Frederick J, Duncan John A, Chodobski Adam
Department of Clinical Neurosciences, Brown University School of Medicine, Providence, Rhode Island 02903, USA.
J Neurotrauma. 2004 Aug;21(8):1090-102. doi: 10.1089/0897715041651033.
Experimental evidence obtained in various animal models of brain injury indicates that vasopressin promotes the formation of cerebral edema. However, the molecular and cellular mechanisms underlying this vasopressin action are not fully understood. In the present study, we analyzed the temporal changes in expression of vasopressin V1a receptors after traumatic brain injury (TBI) in rats. In the intact brain, the V1a receptor was expressed in neurons located in all layers of the frontoparietal cortex. The V1a receptor-immunoreactive product was predominantly localized to neuronal nuclei and had both a diffused and punctate staining pattern. The V1a receptors were also expressed in astrocytes, especially in layer 1 of the frontoparietal cortex. In these cells, two distinctive patterns of immunopositive staining for V1a receptors were observed: a diffused cytosolic staining of cell bodies and processes and a clearly punctate staining pattern that was predominantly localized to the astrocytic cell bodies. The real-time reverse-transcriptase polymerase chain reaction analysis of changes in mRNA for the V1a receptor demonstrated that after TBI, there is an early (4 h post-TBI) increase in the number of transcripts in the ipsilateral frontoparietal cortex, when compared to the contralateral hemisphere or the sham-injured rats. This increase in the message was followed by the up-regulation of expression of the V1a receptors at the protein level. This was most evident in cortical astrocytes in the areas surrounding the lesion. The number of the V1a receptor-immunopositive astrocytes in the traumatized parenchyma gradually increased, starting at 8 h and peaking at 4-6 days after TBI. Furthermore, a redistribution of V1a receptors from the astrocytic cell bodies to the astrocytic processes was observed. In addition to astrocytes, an increased expression of V1a receptors was found in the endothelium of both blood microvessels and the large-diameter blood vessels in the frontoparietal cortex ipsilateral to injury. This increase in the V1a receptor expression was apparent between 2 and 4 days after TBI. As early as 1-2 h following the impact, there was also a striking increase in the number of the V1a receptor-immunopositive beaded axonal processes, with greatly enlarged varicosities, that were localized to various areas of the injured parenchyma. It is suggested that the increased expression of V1a receptors plays an important role in the vasopressin-mediated formation of edema in the injured brain.
在各种脑损伤动物模型中获得的实验证据表明，血管加压素会促进脑水肿的形成。然而，这种血管加压素作用背后的分子和细胞机制尚未完全明确。在本研究中，我们分析了大鼠创伤性脑损伤（TBI）后血管加压素V1a受体表达的时间变化。在完整大脑中，V1a受体表达于位于额顶叶皮质各层的神经元中。V1a受体免疫反应产物主要定位于神经元细胞核，呈现出弥漫性和点状染色模式。V1a受体也表达于星形胶质细胞中，尤其是在额顶叶皮质的第1层。在这些细胞中，观察到V1a受体免疫阳性染色的两种不同模式：细胞体和突起的弥漫性胞质染色以及主要定位于星形胶质细胞体的明显点状染色模式。对V1a受体mRNA变化的实时逆转录聚合酶链反应分析表明，与对侧半球或假手术损伤大鼠相比，TBI后，同侧额顶叶皮质转录本数量在早期（TBI后4小时）增加。这种信息增加之后是V1a受体蛋白水平表达的上调。这在损伤周围区域的皮质星形胶质细胞中最为明显。创伤实质中V1a受体免疫阳性星形胶质细胞的数量从8小时开始逐渐增加，在TBI后4 - 6天达到峰值。此外，还观察到V1a受体从星形胶质细胞体重新分布到星形胶质细胞突起。除了星形胶质细胞外，在损伤同侧额顶叶皮质的微血管和大直径血管内皮中也发现V1a受体表达增加。V1a受体表达的这种增加在TBI后2至4天明显。早在撞击后1 - 2小时，定位于损伤实质各个区域的V1a受体免疫阳性串珠状轴突过程的数量也显著增加，静脉曲张明显增大。提示V1a受体表达增加在血管加压素介导的损伤脑内水肿形成中起重要作用。
