Overexpression of aquaporin-1 aggravates hippocampal damage in mouse traumatic brain injury models

Abstract

'Secondary insult' following primary traumatic brain injury (TBI), including ischemia and edema, may aggravate brain impairments and affect the outcomes. The hippocampus is particularly sensitive to ischemia or edema due to its selective vulnerability, as neural cells of the hippocampus may be more prone to abnormal function or cell death in response to ischemia and edema. Aquaporin‑1 (AQP‑1) was reported to be associated with cerebral edema; however, the expression and role of AQP‑1 in hippocampal edema following TBI have seldom been investigated. In the current study, BALB/c mouse closed craniocerebral injury models were established and the changes of AQP‑1 expression in hippocampi of mouse models following TBI were investigated. Neurological function and edema formation of the models were evaluated and the apoptotic hippocampal cells were then stained in situ and detected, followed by determination of AQP‑1 expression in the hippocampus using immunohistochemistry and western blot analysis. As a result, the majority of mice in the TBI group were severely injured and hippocampal edema was confirmed. The apoptotic cells increased significantly in the hippocampi of mice in the TBI group compared with those in the sham group (P<0.01) and the apoptotic rate increased gradually in a time‑dependent manner. The expression levels of AQP‑1 in the hippocampi of mice were markedly higher in the TBI group than in the sham group (P<0.05) at various time points and AQP‑1 expression levels peaked one day following TBI. These results indicate that upregulation of AQP‑1 may participate in edema formation and delayed cell death of the hippocampus following TBI and may also be a novel therapeutic target to protect the hippocampus from secondary injury following TBI.

Dehydroascorbic Acid Attenuates Ischemic Brain Edema and Neurotoxicity in Cerebral Ischemia: An in vivo Study

“…Specifically AQP-1 is permeable only to water and is considered to participate in brain water homeostasis [54]. In addition, AQP 1 has been reported that it is involved in edema formation and cell death in the hippocampus following brain injury [55]. Following our results, we suggest that DHA may reduce osmotic water permeability following cerebral ischemia by inhibiting the expression of AQP-1.…”

Gut microbiota regulates mouse behaviors through glucocorticoid receptor pathway genes in the hippocampus

“…Aquaporins (AQPs) are the water channels that can transport water across cell membrane in many tissues 36 . Upregulation of Aquaporin 1 (AQP1) caused hippocampal cell edema and delayed cell death following traumatic brain injury 37 , showing that sometimes it protects against neuronal cell damage 38 . However, AQP1 protein overexpression was associated with vacuolization in the astroglial cytoplasm in CA1 astrocytes, which may cause cell apoptosis 39 .…”

Effects of AQP5 gene silencing on proliferation, migration and apoptosis of human glioma cells through regulating EGFR/ERK/ p38 MAPK signaling pathway

“…In addition, AQP5 gene silencing inhibits the proliferation of endometrial glandular epithelial cells notably [18], suggesting that altered AQP5 expression plays a crucial role in tumor progression. Up-regulation of Aquaporin1 (AQP1) gene has been reported to promote the invasiveness of glioma cells [19, 20]. However, the role of AQP5 gene expression in glioma has not been studied.…”