Lack of Aquaporin 9 Reduces Brain Angiogenesis and Exaggerates Neuronal Loss in the Hippocampus Following Intracranial Hemorrhage in Mice
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Intracranial hemorrhage (ICH) is a common subtype of stroke with high morbidity and mortality. However, few clinical therapies that can reduce ICH-induced brain injury and promote the recovery outcome in ICH patients are available to improve the recovery from ICH. Given that aquaporin 9 (AQP9) plays a critical role in brain edema after ischemic stroke and traumatic brain injury and is involved in the regulation of angiogenesis, we examined the role of AQP9 in preventing neuronal loss and in neovascularization in the dorsal hippocampus (DH) after ICH. We found that intra-DH collagenase-induced ICH increased AQP9 protein levels in the hippocampus, which was associated with behavioral deficits in wild-type mice. However, ICH robustly enhanced behavioral deficits in the AQP9-null mice, as compared with the wild-type mice. Furthermore, neovascularization and proliferation of brain microvascular endothelial cells following ICH were severely impaired in the AQP9-null mice, as compared with the wild-type mice. Finally, hippocampal neuronal loss following ICH became severer in the AQP9-null mice, relative to the wild-type mice. Taken together, our findings indicated that AQP9 in the brain may play a compensatory role in response to ICH, promote brain angiogenesis, and prevent subsequent neuronal death, thus preventing the deterioration of neurological outcome of ICH.
KeywordsIntracranial hemorrhage Angiogenesis Aquaporin 9 Hippocampus Neuronal loss
Compliance with Ethical Standards
All animal experiments were approved by the Institutional Animal Care and Use Committee of Wuxi No. 2 Hospital. The housing and treatment of the mice followed the guidelines of the “Guide for the Care and Use of Laboratory Animals” (Institute of Laboratory Animal Resources, Commission on Life Sciences 2011). All efforts were made to minimize suffering.
This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.
Conflict of Interest
The authors declare that they have no conflict of interest.
All applicable international, national, and institutional guidelines for the care and use of animals were followed.
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