Targeting Water in the Brain: Role of Aquaporin-4 in Ischemic Brain Edema

Brain edema primarily occurs as a consequence of various cerebral injuries including ischemic stroke. Excessive accumulation of brain water content causes a gradual expansion of brain parenchyma, decreased blood flow and increased intracranial pressure and, ultimately, cerebral herniation and death. Current clinical treatment for ischemic edema is very limited, therefore, it is urgent to develop novel treatment strategies. Mounting evidence has demonstrated that AQP4, a water channel protein, is closely correlated with brain edema and could be an optimal therapeutic target for the reduction of ischemic brain edema. AQP4 is prevalently distributed in the central nervous system, and mainly regulates water flux in brain cells under normal and pathological conditions. This review focuses on the underlying mechanisms of AQP4 related to its dual role in edema formation and elimination.

Download Full-text

Ischemic Brain Edema: Influence of Ischemia Duration on Edema Formation

Brain Edema ◽

10.1007/978-3-642-70696-7_63 ◽

1985 ◽

pp. 424-429 ◽

Cited By ~ 1

Author(s):

K. Aritake ◽

M. Brock

Keyword(s):

Brain Edema ◽

Edema Formation ◽

Ischemic Brain ◽

Ischemic Brain Edema

Download Full-text

Attenuation of Ischemic Brain EDEMA and Cerebrovascular Injury after Ischemic Preconditioning in the Rat

Journal of Cerebral Blood Flow & Metabolism ◽

10.1097/00004647-200101000-00004 ◽

2001 ◽

Vol 21 (1) ◽

pp. 22-33 ◽

Cited By ~ 89

Author(s):

Tetsuya Masada ◽

Ya Hua ◽

Guohua Xi ◽

Steven R. Ennis ◽

Richard F. Keep

Keyword(s):

Brain Edema ◽

Blood Brain Barrier ◽

Vascular Injury ◽

Ischemic Preconditioning ◽

Dry Weight ◽

Sham Operation ◽

Edema Formation ◽

Ischemic Brain ◽

Ischemic Brain Edema ◽

Brain Edema Formation

Ischemic preconditioning (IPC) induces neuroprotection to subsequent severe ischemia, but its effect on the cerebrovasculature has not been studied extensively. This study evaluated the effects of IPC on brain edema formation and endothelial cell damage that follows subsequent permanent focal cerebral ischemia in the rat. Transient (15 minute) middle cerebral artery occlusion (MCAO) was used for IPC. Three days after IPC or a sham operation, permanent MCAO was induced. Twenty-four hours after permanent MCAO, neurologic deficit, infarction volume, and water and ion content were evaluated. Six hours post-ischemia, blood–brain barrier (BBB) permeability was examined using [3H]-inulin. Water, ion contents, and BBB permeability were assessed in three zones (core, intermediate, and outer) depending on their relation to the MCA territory. Heat shock protein 70 (HSP70) was also examined as a potential marker of vascular injury. The model of IPC significantly reduced brain infarction and neurologic deficit. Compared with a sham operation, IPC also significantly attenuated brain edema formation in the intermediate (sham and IPC water contents: 5.99 ± 0.65 vs. 4.99 ± 0.81 g/g dry weight; P < 0.01) and outer zones (5.02 ± 0.48 vs. 4.37 ± 0.42 g/g dry weight; P < 0.01) of the ipsilateral hemisphere but not in the core zone. Blood–brain barrier disruption assessed by [3H]-inulin was significantly attenuated in the IPC group and the number of blood vessels that displayed HSP70 immunoreactivity was also reduced. Thus, IPC significantly attenuates ischemic brain edema formation, BBB disruption, and, as assessed by HSP70, vascular injury. Understanding the mechanisms involved in IPC may provide insight into methods for preserving cerebrovascular function during ischemia.

Download Full-text