Hydrocephalus: the role of cerebral aquaporin-4 channels and modeling considerations of cerebrospinal fluid
Hydrocephalus: the role of cerebral aquaporin-4 channels and modeling considerations of cerebrospinal fluid
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DOI：
10.3171/2016.7.focus16191
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发表时间：
2016-09-01
影响因子：
4.1
通讯作者：
Linninger, Andreas
中科院分区：
文献类型：
--
作者：
Desai, Bhargav;Hsu, Ying;Linninger, Andreas
水通道蛋白4(Aquaporin-4，AQP4)通道在脑内水平衡中起着重要作用。水跨膜转运在正常和病变脑组织的脑水交换中起着至关重要的作用。AQP4通道与脑积水的病理生理学有关，脑积水是一种水分失衡的疾病，导致脑室系统中的脑脊液积聚。脑积水时液体交换的许多分子方面尚未明确阐明，但回顾文献表明，调节AQP4通道活性是一种潜在的有吸引力的未来药物治疗方法。以水通道为靶点的药物治疗可以控制水交换，通过分子干预而不是机械分流来清除多余的脑脊液。本文就AQP4通道与脑积水的关系、AQP4通道分子方面的细节、可能的药物开发策略和局限性等方面的大量文献进行综述。本文综述了脑积水的医学影像和脑脊液动力学计算模型的研究进展。计算建模中的算法发展继续加深对脑积水疾病过程的理解，并显示出作为内科医生评估脑积水患者的工具的潜在好处。
Aquaporin-4 (AQP4) channels play an important role in brain water homeostasis. Water transport across plasma membranes has a critical role in brain water exchange of the normal and the diseased brain. AQP4 channels are implicated in the pathophysiology of hydrocephalus, a disease of water imbalance that leads to CSF accumulation in the ventricular system. Many molecular aspects of fluid exchange during hydrocephalus have yet to be firmly elucidated, but review of the literature suggests that modulation of AQP4 channel activity is a potentially attractive future pharmaceutical therapy. Drug therapy targeting AQP channels may enable control over water exchange to remove excess CSF through a molecular intervention instead of by mechanical shunting. This article is a review of a vast body of literature on the current understanding of AQP4 channels in relation to hydrocephalus, details regarding molecular aspects of AQP4 channels, possible drug development strategies, and limitations. Advances in medical imaging and computational modeling of CSF dynamics in the setting of hydrocephalus are summarized. Algorithmic developments in computational modeling continue to deepen the understanding of the hydrocephalus disease process and display promising potential benefit as a tool for physicians to evaluate patients with hydrocephalus.