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

Abstract

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 of MMP-2 and MMP-9 in the plasma of patients with moderate or severe TBI and in the brain extracellular fluid (ECF). Prospective observational study. Neurotraumatology intensive care unit of a tertiary university hospital. 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. Plasma samples were collected within the first 12[Symbol: see text]h and at 24[Symbol: see text]h post-injury. Simultaneous brain microdialysate and plasma samples were obtained in four moderate-severe TBI patients at additional timepoints: 48, 72, and 96[Symbol: see text]h post-TBI. 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[Symbol: see text]h post-injury. Brain microdialysis samples presented a similar time profile as plasma samples for both gelatinases. 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.