The effects of protein kinase C activator phorbol dibutyrate on traumatic brain edema and aquaporin-4 expression.

BACKGROUND

Aquaporin-4 (AQP4) is the major water channel in the central nervous system. Brain edema emerges from increased AQP4 expression in traumatic brain injury (TBI). Cell line studies have shown that the protein kinase activator phorbol ester exerts a suppressive effect on AQP4 and water permeability. The aim of this study was to investigate the effects of a phorbol ester, phorbol dibutyrate (PDBu), on increased TBI AQP4 expression and accompanying brain edema.

METHODS

Fifty-six male Wistar rats were first divided into two groups: the edema group, in which the percentage of water in brain tissue would be evaluated, and the immunohistochemical group, allowing AQP4 expression to be determined. Both groups were further sub-divided into four groups consisting of 7 subjects. These four groups were as follows: sham-operated control group, severe diffuse TBI group, 0.9% saline-treated diffuse TBI group, and the PDBu-treated diffuse TBI group (2300 µg/kg, iv). The results were evaluated statistically.

RESULTS

PDBu treatment significantly reduced brain water concentration (p<0.001). Furthermore, PDBu was found to reduce trauma-induced AQP4 upregulation (p<0.05).

CONCLUSIONS

This study showed that traumatic brain edema was prevented by intravenous PDBu administration via AQP4 downregulation, supporting the idea emphasizing the importance of AQP4 expression control in TBI.