Document Detail


Increases in cerebrospinal fluid caffeine concentration are associated with favorable outcome after severe traumatic brain injury in humans.
MedLine Citation:
PMID:  17684518     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Caffeine, the most widely consumed psychoactive drug and a weak adenosine receptor antagonist, can be neuroprotective or neurotoxic depending on the experimental model or neurologic disorder. However, its contribution to pathophysiology and outcome in traumatic brain injury (TBI) in humans is undefined. We assessed serial cerebrospinal fluid (CSF) concentrations of caffeine and its metabolites (theobromine, paraxanthine, and theophylline) by high-pressure liquid chromatography/ultraviolet in 97 ventricular CSF samples from an established bank, from 30 adults with severe TBI. We prospectively selected a threshold caffeine level of > or = 1 micromol/L (194 ng/mL) as clinically significant. Demographics, Glasgow Coma Scale (GCS) score, admission blood alcohol level, and 6-month dichotomized Glasgow Outcome Scale (GOS) score were assessed. Mean time from injury to initial CSF sampling was 10.77+/-3.13 h. On initial sampling, caffeine was detected in 24 of 30 patients, and the threshold was achieved in 9 patients. Favorable GOS was seen more often in patients with CSF caffeine concentration > or = versus < the threshold (55.6 versus 11.8%, P=0.028). Gender, age, admission CGS score, admission blood alcohol level, and admission systolic arterial blood pressure did not differ between patients with CSF caffeine concentration > or = versus < the threshold. Increases in CSF concentrations of the caffeine metabolites theobromine and paraxanthine were also associated with favorable outcome (P=0.018 and 0.056, respectively). Caffeine and its metabolites are commonly detected in CSF in patients with severe TBI and in an exploratory assessment are associated with favorable outcome. We speculate that caffeine may be neuroprotective by long-term upregulation of adenosine A1 receptors or acute inhibition of A2a receptors.
Authors:
Kathleen T Sachse; Edwin K Jackson; Stephen R Wisniewski; Delbert G Gillespie; Ava M Puccio; Robert S B Clark; C Edward Dixon; Patrick M Kochanek
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2007-08-08
Journal Detail:
Title:  Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism     Volume:  28     ISSN:  0271-678X     ISO Abbreviation:  J. Cereb. Blood Flow Metab.     Publication Date:  2008 Feb 
Date Detail:
Created Date:  2008-01-25     Completed Date:  2008-04-17     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8112566     Medline TA:  J Cereb Blood Flow Metab     Country:  United States    
Other Details:
Languages:  eng     Pagination:  395-401     Citation Subset:  IM    
Affiliation:
Department of Critical Care Medicine, Safar Center for Resuscitation Research, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15260, USA.
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MeSH Terms
Descriptor/Qualifier:
Adult
Aging / physiology
Brain Injuries / cerebrospinal fluid*
Caffeine / cerebrospinal fluid*
Central Nervous System Depressants / blood
Central Nervous System Stimulants / cerebrospinal fluid*
Ethanol / blood
Female
Glasgow Coma Scale
Glasgow Outcome Scale
Humans
Male
Prospective Studies
Theobromine / cerebrospinal fluid
Theophylline / cerebrospinal fluid
Treatment Outcome
Grant Support
ID/Acronym/Agency:
DK68575/DK/NIDDK NIH HHS; NS30318/NS/NINDS NIH HHS; NS38087/NS/NINDS NIH HHS
Chemical
Reg. No./Substance:
0/Central Nervous System Depressants; 0/Central Nervous System Stimulants; 58-08-2/Caffeine; 58-55-9/Theophylline; 611-59-6/1,7-dimethylxanthine; 64-17-5/Ethanol; 83-67-0/Theobromine

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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