Effects of Different Doses of Levetiracetam on Aquaporin 4 Expression in Rats with Brain Edema Following Fluid Percussion Injury
Hongbo Jin, Wenling Li, Changzheng Dong, Li Ma, Jiang Wu, Wenqing Zhao
Faculty of Graduate Studies, Hebei Medical University, Shijiazhuang, Hebei, China (mainland)
Med Sci Monit 2016; 22:678-686
Available online: 2016-02-29
This study was designed to investigate the effects of different doses of levetiracetam on aquaporin 4 (AQP4) expression in rats after fluid percussion injury.
MATERIAL AND METHODS: Sprague-Dawley rats were randomly divided into 4 groups: sham operation group, traumatic brain injury group, low-dose levetiracetam group, and high-dose levetiracetam group. Brain edema models were established by fluid percussion injury, and intervened by the administration of levetiracetam. Samples from the 4 groups were collected at 2, 6, 12, and 24 h, and at 3 and 7 days after injury. Histological observation was performed using hematoxylin-eosin staining and immunohistochemical staining. AQP4 and AQP4 mRNA expression was detected using Western blot assay and RT-PCR. Brain water content was measured by the dry-wet method.
RESULTS: Compared with the traumatic brain injury group, brain water content, AQP4 expression, and AQP4 mRNA expression were lower in the levetiracetam groups at each time point and the differences were statistically significant (P<0.05). The intervention effects of high-dose levetiracetam were more apparent.
CONCLUSIONS: Levetiracetam can lessen brain edema from fluid percussion injury by down-regulating AQP4 and AQP4 mRNA expression. There is a dose-effect relationship in the preventive effect of levetiracetam within a certain extent.
Keywords: Aquaporin 4 - metabolism, Animals, Blotting, Western, Brain - pathology, Brain Edema - genetics, Brain Injuries - genetics, Dose-Response Relationship, Drug, Gene Expression Regulation - drug effects, Percussion, Piracetam - therapeutic use, RNA, Messenger - metabolism, Rats, Sprague-Dawley, Real-Time Polymerase Chain Reaction, Water - metabolism