Expression and roles of aquaporin 1 in hippocampus of mice model with traumatic brain injury

Abstract

Background The "secondary brain insult" including ischemia, hypoxia and edema after primary traumatic brain injury (TBI) may deteriorate the brain damages and greatly influence the prognosis. As a selective vulnerable region, the hippocampus is especially sensitive to ischemia, hypoxia or edema and yields irreversible sequelae. Aquaporin 1 (AQP1) has been reported to be related to cerebral edema, but the expression and role of AQP1 in hippocampal edema after TBI have seldomly been investigated. In this study, we established BALB/c mouse closed craniocerebral injury models and investigated the changes of AQP1 expression in hippocampus of mouse models after TBI, thereby discussing its effects on relevant pathophysiological processes. Methods Seventy-five BALB/c mice were used to establish experimental closed TBI models with a free-falling weight drop device, and the equal numbers of mice were subject to sham operation and categorized as sham group. The neurological function of each mouse in either TBI group or sham group was scored at different time points (1, 6, 24 and 72 h) after TBI or sham operation, and brain edema formation of the mice in both groups was also evaluated accordingly at 6, 24 and 72 h. The apoptotic hippocampal cells were stained in situ and detected using TdT-mediated dUTP-biotin nick end labeling (TUNEL) method at different time points (6, 24 and 72 h), then AQP1 expression in hippocampus was also correspondingly detected using immunohistochemistry and Western blotting. All the data were finally compared with those in sham operation group and analyzed. Results Experimental TBI models were successfully established and confirmed by the neurological function score and hippocampal edema evaluation. Six hours after craniocerebral injury, the apoptotic cells increased significantly in the hippocampus of mice in TBI group compared with those in sham group [(44.26 ± 15.18)% vs (8.61 ± 8.25)% , t = - 9.676, P = 0.002]. The apoptotic rate increased gradually with the prolonging of time and was highest at 72 h [(61.62 ± 26.55)% vs (10.17 ± 6.08)%; t = - 5.018, P = 0.015]. Determined at different time points by immunohistochemistry and Western blotting assays, the AQP1 expression in mouse hippocampus was constantly higher in TBI group than in sham group ( P < 0.05), and reached the peak at 24 h (0.69 ± 0.32 vs 0.15 ± 0.07, t = - 4.335, P = 0.023 and 0.46 ± 0.19 vs 0.14 ± 0.04, t = - 4.113, P = 0.004, respectively). Conclusions The up-regulation of AQP1 in mouse hippocampus after TBI perhaps participates in edema formation and delayed apoptosis of hippocampus, and AQP1 may be a new therapeutic target to protect hippocampus from secondary injury after TBI. doi: 10.3969/j.issn.1672-6731.2014.03.016