Combinatorial therapy with two pro-coagulants and one osmotic agent reduces the extent of the lesion in the acute phase of spinal cord injury in the rat

Mathieu Boutonnet, Elisabeth Laemmel, Eric Vicaut, Jacques Duranteau, Marc Soubeyrand

Spinal cord injury (SCI) is a complex disease that leads to a motor, sensitive, and vegetative impairment. So far, single therapies are ineffective for treating SCI in humans and a multifactorial therapeutic approach may be required. The aim of this work was to assess the effect of a triple therapy (TT) associating two pro-coagulant therapies (tranexamic acid and fibrinogen) with an anti-edema therapy (hypertonic saline solution), on the extent of the lesion 24 h post-injury. The design of this study is a randomized controlled study. The setting of this study is an experimental study. Male Wistar rats were assigned to receive saline solution for the control group or one of the treatment, or a combination of two treatments or the three treatments (triple therapy group (TT)). Animals were anesthetized and received a weight-drop SCI induced at the level of the 12th thoracic vertebra (Th12). They were treated by single therapies, double therapies, or TT started 5 min after the SCI. The extent of the lesion was assessed 24 h after injury by spectrophotometry (quantification of parenchymal hemorrhage and blood-spinal cord barrier disruption) and by histology (quantification of spared neuronal tissue). As compared with the control group, the TT significantly reduced parenchymal hemorrhage (p < 0.05) and improved the total amount of intact neural tissue, measured 24 h later (p = 0.003). Combinatorial therapy associating two pro-coagulants (tranexamic acid and fibrinogen) with an anti-edema therapy (hypertonic saline solution) reduces the extent of the lesion in the acute phase of spinal cord injury in the rat.