Combined effect of trifluoperazine and sodium cromoglycate on reducing acute edema and limiting lasting functional impairments after spinal cord injury in rats

Edema formation is one of the very first events to occur after spinal cord injury (SCI) leading to an increase of the intrathecal pressure and consequently to serious spinal tissue and functional impairments. Current edema treatments are still symptomatic and/or non-specific. Since edema formation mechanisms are mainly described as vasogenic and cytotoxic, it becomes crucial to understand the interplay between these two subtypes. Acting on key targets to inhibit edema formation may reduce secondary damage and related functional impairments. In this study, we characterize the edema kinetic after T9-10 spinal contusion. We use trifluoperazine (TFP) to block the expression and the functional subcellular localization of aquaporin-4 supposed to be implicated in the cytotoxic edema formation. We also use sodium cromoglycate (SCG) to deactivate mast cell degranulation known to be implicated in the vasogenic edema formation. Our results show a significant reduction of edema after TFP treatment and after TFP-SCG combined treatment compared to control. This reduction is correlated with limited onset of initial sensorimotor impairments particularly after combined treatment. Our results highlight the importance of potential synergetic targets in early edema therapy after SCI as part of tissue sparing strategies.