Differential Upregulation of Aquaporin-4 mRNA Expression in Reactive Astrocytes after Brain Injury: Potential Role in Brain Edema

Differential Upregulation of Aquaporin-4 mRNA Expression in Reactive Astrocytes after Brain Injury: Potential Role in Brain Edema
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DOI:
10.1006/nbdi.1999.0246
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发表时间:
1999-08
影响因子:
6.1
通讯作者:
Marisa Vizuete;J. L. Venero;Carmen Vargas;Anunciación A. Ilundáin;M. Echevarra;A. Machado;J. Cano
Marisa Vizuete;J. L. Venero;Carmen Vargas;Anunciación A. Ilundáin;M. Echevarra;A. Machado;J. Cano
中科院分区:
医学1区
文献类型:
--
作者:
Marisa Vizuete;J. L. Venero;Carmen Vargas;Anunciación A. Ilundáin;M. Echevarra;A. Machado;J. Cano

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星形胶质细胞和水通道蛋白4(AQP4)在脑离子稳态中起重要作用。因此,在不同的神经损伤后,在中枢神经系统中的AQP4 mRNA的调节是感兴趣的。单次纹状体内注射林格或喹啉酸强烈诱导AQP4 mRNA在纹状体,特别是在病变的核心。共定位研究表明,AQP4 mRNA的诱导仅限于肥大的星形胶质细胞。纹状体AQP4 mRNA诱导的程度与神经元变性无关,但与作为血脑屏障破坏标志物的伊文思蓝染料外渗有关。通过6-OHDA或内侧前脑束(MFB)中的刀切割额外诱导远处病变。前者,而不是后者,诱导高AQP4 mRNA的表达在受损的黑质。然而,轴突切断的MFB诱导高AQP4 mRNA的表达在病变部位。我们的结论是,水通道蛋白4 mRNA的表达的诱导有关的血脑屏障的破坏和脑水肿条件下,这个水通道在重建脑渗透平衡中起着关键作用。
Astrocytes and aquaporin-4 (AQP4) play a significant role in brain ion homeostasis. Consequently the regulation of AQP4 mRNA in the CNS after different neurological insults was of interest. A single intrastriatal injection of ringer or quinolinic acid strongly induced AQP4 mRNA in the striatum, specially at the core of the lesion. Colocalization studies demonstrated that AQP4 mRNA induction was restricted to hypertrophic astrocytes. The extent of striatal AQP4 mRNA induction did not correlate with neuronal degeneration, but it did with extravasation of Evans blue dye as a marker of BBB disruption. Distant lesions were additionally induced by either 6-OHDA or a knife cut in the medial forebrain bundle (MFB). The former, but not the latter, induced a high AQP4 mRNA expression in the lesioned substantia nigra. However, axotomy of the MFB induced a high AQP4 mRNA expression at the lesion site. We conclude that the induction of AQP4 mRNA expression is related to disruption of the blood-brain barrier and under brain edema conditions this water channel plays a key role in the reestablishment of the brain osmotic equilibrium.