Brain metabolic and hemodynamic effects of cyclosporin A after human severe traumatic brain injury: a microdialysis study
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- 作者：Anna Teresa Mazzeo (1) (2)
óscar Luís Alves (3)
Charlotte B. Gilman (2)
Ronald L. Hayes (4) (5)
Christos Tolias (6)
K. Niki Kunene (7)
M. Ross Bullock (8) - 关键词：Cyclosporin A ; Neuroprotection ; Traumatic brain injury ; Cerebral microdialysis ; Cerebral hemodynamics
- 刊名：Acta Neurochirurgica
- 出版年：2008
- 出版时间：October 2008
- 年：2008
- 卷：150
- 期：10
- 页码：1019-1031
- 全文大小：518KB
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óscar Luís Alves (3)
Charlotte B. Gilman (2)
Ronald L. Hayes (4) (5)
Christos Tolias (6)
K. Niki Kunene (7)
M. Ross Bullock (8)
1. Department of Neuroscience, Psychiatric and Anesthesiological Sciences, University of Messina, Viale Regina Margherita n. 59, 98121, Messina, Italy
2. Division of Neurosurgery, Medical College of Virginia, Virginia Commonwealth University, Richmond, VA, USA
3. Servi?o de Neurocirurgia, Centro Hospitalar de Vila Nova de Gaia, Faculdade de Medicina da Universitade do Porto, Porto, Portugal
4. Department of Anesthesiology, University of Florida, Gainesville, FL, USA
5. Center of Innovative Research, Banyan Biomarkers, Inc., Alachua, FL, USA
6. Department of Neurosurgery, Kings College Hospital, London, UK
7. Department of Computer Information Systems, University of Louisville, Louisville, KY, USA
8. Department of Neurosurgery, University of Miami Miller School of Medicine, Lois Pope LIFE Center, Miami, FL, USA
文摘
Background Mitochondrial dysfunction is a major limiting factor in neuronal recovery following traumatic brain injury. Cyclosporin A (CsA) has been recently proposed for use in the early phase after severe head injury, for its ability to preserve mitochondrial bioenergetic state, potentially exerting a neuroprotective effect. The aim of this study was, therefore, to evaluate the effect of CsA on brain energy metabolism, as measured by cerebral microdialysis, and on cerebral hemodynamics, in a group of severely head injured patients. Methods Fifty adult patients with a severe head injury were enrolled in this randomized, double-blind, placebo-controlled study. Patients received 5?mg/kg of CsA over 24?h, or placebo, within 12?h of the injury. A microdialysis probe was placed in all patients, who were managed according to standard protocols for the treatment of severe head injury. Findings The most robust result of this study was that, over most of the monitoring period, brain dialysate glucose was significantly higher in the CsA treated patients than in placebo. Both lactate and pyruvate were also significantly higher in the CsA group. Glutamate concentration and lactate/pyruvate ratio were significantly higher in the placebo group than in CsA treated patients, respectively 1 to 2?days, and 2 to 3?days after the end of the 24-h drug infusion. The administration of CsA was also associated with a significant increase in mean arterial pressure (MAP) and cerebral perfusion pressure (CPP). Conclusions The administration of CsA in the early phase after head injury resulted in significantly higher extracellular fluid glucose and pyruvate, which may be evidence of a beneficial effect. The early administration of CsA was also associated with a significant increase in MAP and CPP and such a potentially beneficial hemodynamic effect might contribute to a neuroprotective effect.