Effects of Aquaporin 4 Knockdown on Brain Edema of the Uninjured Side After Traumatic Brain Injury in Rats
Jian-Qiang Chen, Cheng-Cheng Zhang, Sheng-Nan Jiang, Hong Lu, Wei Wang
Department of Radiology, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China (mainland)
Med Sci Monit 2016; 22:4809-4819
Available online: 2016-12-08
Traumatic brain injury (TBI) induces edema on the uninjured side (i.e., contralateral brain tissue; CBT). We evaluated the role of AQP4 in CBT edema formation following TBI.
MATERIAL AND METHODS: Mild or severe TBI was induced using a controlled cortical impact model in rats, immediately followed by intraventricular siRNA infusions. The effects of AQP4 siRNA on CBT edema were assessed at up to 168 h.
RESULTS: Mild or severe TBI induced different patterns of CBT edema. Furthermore, following mild TBI, brain water content (BWC) was increased at 72 h thereafter and AQP4 expression was increased after 168 h, relative to non-injured rats (i.e., sham). AQP4 interference reduced AQP4 expression 48 h thereafter and BWC 72 h thereafter, relative to control siRNA. In contrast, following severe TBI, BWC was increased 1 h thereafter and AQP4 expression was transiently enhanced after 1 h, relative to sham. However, AQP4 interference reduced AQP4 expression after 1 h and BWC 24 h thereafter, relative to control siRNA. Finally, apparent diffusion coefficient (ADC) value in CBT was positively correlated with AQP4 expression level following severe, but not mild, TBI. AQP4 interference disrupted this correlation.
CONCLUSIONS: AQP4 interference reduces CBT edema formation, and ADC value may predict TBI severity.
Keywords: Brain Edema - metabolism, Aquaporin 4 - metabolism, Animals, Brain Injuries - metabolism, Brain Injuries, Traumatic - therapy, Disease Models, Animal, Gene Expression Profiling, Gene Knockdown Techniques, RNA, Small Interfering - genetics, Random Allocation, Rats, Rats, Sprague-Dawley