Brain metabolic and hemodynamic effects of cyclosporin A after human severe traumatic brain injury: a microdialysis study.
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.


RESULTS
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.
Mazzeo
Anna Teresa
AT
Department of Neuroscience, Psychiatric and Anesthesiological Sciences, University of Messina, Viale Regina Margherita n. 59, 98121 Messina, Italy. annateresamazzeo@unime.it
Alves
Oscar Luís
OL
Gilman
Charlotte B
CB
Hayes
Ronald L
RL
Tolias
Christos
C
Niki Kunene
K
K
Ross Bullock
M
M
D000328:Adult; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D001930:Brain Injuries / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D002560:Cerebrovascular Circulation / Q000187:drug effects* / Q000502:physiology; D016572:Cyclosporine / Q000008:administration & dosage*; D004311:Double-Blind Method; D004734:Energy Metabolism / Q000187:drug effects* / Q000502:physiology; D045604:Extracellular Fluid / Q000187:drug effects / Q000378:metabolism; D005260:Female; D005947:Glucose / Q000378:metabolism; D006801:Humans; D008297:Male; D017551:Microdialysis / Q000379:methods; D008875:Middle Aged; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D018696:Neuroprotective Agents / Q000008:administration & dosage*; D010919:Placebos; D019289:Pyruvic Acid / Q000378:metabolism; D016896:Treatment Outcome; D055815:Young Adult
D018696:Neuroprotective Agents; D010919:Placebos; D016572:Cyclosporine; D019289:Pyruvic Acid; D005947:Glucose