Moderate and severe traumatic brain injury induce early overexpression of systemic and brain gelatinases

Objective: Recent experimental evidence suggests that matrix metalloproteinases (MMPs) are implicated in the pathophysiology of traumatic brain injury (TBI) by increasing blood-brain barrier permeability and exacerbating posttraumatic edema. We examined the acute profile ofMMP- 2 and MMP-9 in the plasma of patients with moderate or severe TBI and in the brain extracellular fluid (ECF). Design: Prospective observational study. Setting: Neurotraumatology intensive care unit of a tertiary university hospital. Patients: Twenty patients with moderate or severe TBI were included and three groups were used as controls: 20 patients with a mild head injury and normal CT scan, 15 moderate polytrauma patients without TBI, and 20 healthy volunteers. Interventions: Plasma samples were collected within the first 12 h and at 24 h post-injury. Simultaneous brain microdialysate and plasma samples were obtained in four moderate-severe TBI patients at additional timepoints: 48, 72, and 96 h post-TBI. Measurements and main results: Gelatinases (MMP-2 and MMP-9) were measured by gelatin zymography. A significant increase in plasma gelatinases was observed at baseline when compared with healthy volunteers in the study group. This early increase was followed by a significant decrease at 24 h post-injury. Brain microdialysis samples presented a similar time profile as plasma samples for both gelatinases. Conclusions: High levels of gelatinases were found in plasma and brain ECF in the early phase of TBI, indicating that both local and systemic trauma-induced upregulation of gelatinases in the acute phase might play an important role in the pathophysiology of TBI and could be a future therapeutic target.