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

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Abstract

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 of MMP-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.

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Acknowledgements

This study was supported by Fondo de Investigaciones Sanitarias de la Seguridad Social (FIS) grant number 05/1092, by the Commission of the European Communities, specific RTD programme ‘Quality of Life and Management of Living Resources’ project QLK6-CT-2002-02583, and by Fundación Mapfre Medicina grant 2004-2005. A Vilalta is the recipient of a pre-doctoral grant from the Institut Fundació de Recerca, Vall d’Hebron University Hospital, Universitat Autònoma de Barcelona, Barcelona, Spain. We are grateful to M. Quintana for statistical advice and to S. Voss for her assistance in translating the manuscript into English.

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Authors and Affiliations

  1. Neurotraumatology and Neurosurgery Research Unit (UNINN), Vall d’Hebron University Hospital, Universitat Autònoma de Barcelona (UAB), Passeig Vall d’Hebron 119-129, 08035, Barcelona, Spain

    Anna Vilalta

  2. Department of Neurosurgery, Vall d’Hebron University Hospital, Universitat Autònoma de Barcelona (UAB), Passeig Vall d’Hebron 119-129, 08035, Barcelona, Spain

    Juan Sahuquillo & Maria A. Poca

  3. Neurovascular Research Laboratory and Neurovascular Unit, Vall d’Hebron University Hospital, Universitat Autònoma de Barcelona (UAB), Passeig Vall d’Hebron 119-129, 08035, Barcelona, Spain

    Anna Rosell & Joan Montaner

  4. Neurotraumatology Intensive Care Unit, Vall d’Hebron University Hospital, Universitat Autònoma de Barcelona (UAB), Passeig Vall d’Hebron 119-129, 08035, Barcelona, Spain

    Marilyn Riveiro

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  1. Anna Vilalta
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  2. Juan Sahuquillo
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  4. Maria A. Poca
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  5. Marilyn Riveiro
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  6. Joan Montaner
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Corresponding author

Correspondence to Juan Sahuquillo.

Additional information

This work was presented, in part, at the 8th International Neurotrauma Symposium, Rotterdam, The Netherlands, 21–25 May 2006.

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Vilalta, A., Sahuquillo, J., Rosell, A. et al. Moderate and severe traumatic brain injury induce early overexpression of systemic and brain gelatinases. Intensive Care Med 34, 1384–1392 (2008). https://doi.org/10.1007/s00134-008-1056-1

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  • DOI: https://doi.org/10.1007/s00134-008-1056-1

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