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大鼠创伤性脑损伤模型中水通道蛋白-4的调控

Regulation of aquaporin-4 in a traumatic brain injury model in rats.

作者信息

Sun Ming-Chieh, Honey Christopher R, Berk Caglar, Wong Norman L M, Tsui Joseph K C

机构信息

Cardinal Tien Hospital and Fu-Jen Catholic University, Taiwan, Republic of China.

出版信息

J Neurosurg. 2003 Mar;98(3):565-9. doi: 10.3171/jns.2003.98.3.0565.

DOI:10.3171/jns.2003.98.3.0565
PMID:12650429
Abstract

OBJECT

Aquaporin-4 (AQP4) plays a significant role in the regulation of brain water homeostasis. In this study the authors investigated the regulation of AQP4 following a focal cortical contusion injury in rats.

METHODS

Thirty-three adult male Wistar rats received a focal cortical contusion of the parietal cortex. An additional nine rats underwent a craniectomy, but no trauma was inflicted (sham injury). Animals were killed 1, 4, and 24 hours later. The rat brains were examined for water content by comparing the wet and dry weights of each hemisphere. Aquaporin-4 messenger (m)RNA was measured by reverse transcription-polymerase chain reaction. A ratio of AQP4 mRNA expression in the lesioned hemisphere compared with that in the contralateral control hemisphere was calculated for each animal at the injury site (parietal cortex) and at sites adjacent to (occipital cortex) and distant from the injury (frontal pole cortex). Brain edema was significantly increased at the injury site. The expression of AQP4 mRNA was significantly increased at the injury site, significantly decreased adjacent to the injury site, and not significantly different at a site distant from the injury. The magnitude of AQP4 mRNA upregulation at the injured parietal cortex correlated with the degree of downregulation in the adjacent occipital cortex.

CONCLUSIONS

Data from this study demonstrate that an upregulation of AQP4 occurs at the site of traumatic brain injury and that a downregulation of this molecule occurs adjacent to the site of injury. Understanding the physiology of AQP4 and its regulation following brain injury may allow for the development of novel treatments for cerebral edema that accompanies head injury.

摘要

目的

水通道蛋白4(AQP4)在调节脑内水平衡中起重要作用。在本研究中,作者调查了大鼠局灶性皮质挫伤损伤后AQP4的调节情况。

方法

33只成年雄性Wistar大鼠接受顶叶皮质的局灶性皮质挫伤。另外9只大鼠接受开颅手术,但未造成创伤(假损伤)。1、4和24小时后处死动物。通过比较每个半球的湿重和干重检查大鼠脑的含水量。通过逆转录-聚合酶链反应测量水通道蛋白4信使核糖核酸(mRNA)。计算每只动物在损伤部位(顶叶皮质)、损伤部位相邻处(枕叶皮质)和远离损伤部位(额叶极皮质)时,损伤半球与对侧对照半球中AQP4 mRNA表达的比值。损伤部位的脑水肿明显增加。损伤部位AQP4 mRNA的表达显著增加,损伤部位相邻处显著降低,远离损伤部位处无显著差异。损伤的顶叶皮质处AQP4 mRNA上调的幅度与相邻枕叶皮质下调的程度相关。

结论

本研究数据表明,创伤性脑损伤部位出现AQP4上调,且该分子在损伤部位相邻处下调。了解AQP4的生理学及其在脑损伤后的调节情况,可能有助于开发针对伴随头部损伤的脑水肿的新治疗方法。

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