Effects of propranolol and clonidine on brain edema, blood-brain barrier permeability, and endothelial glycocalyx disruption after fluid percussion brain injury in the rat

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BACKGROUND: Traumatic brain injury causes a disruption of the vascular endothelial glycocalyx layer that is associated with an overactivation of the sympathoadrenal system. We hypothesized that early and unselective beta-blockade with propranolol alone or in combination with the alfa2-agonist clonidine would decrease brain edema, blood-brain barrier permeability, and glycocalyx disruption at 24 hours after trauma.

METHODS: We subjected 53 adult male Sprague-Dawley rats to lateral fluid percussion brain injury and randomized infusion with propranolol (n = 16), propranolol + clonidine (n = 16), vehicle (n = 16), or sham (n = 5) for 24 hours. Primary outcome was brain water content at 24 hours. Secondary outcomes were blood-brain barrier permeability and plasma levels of syndecan-1 (glycocalyx disruption), cell damage (histone-complexed DNA fragments), epinephrine, norepinephrine, and animal motor function.

RESULTS: We found no difference in brain water content (mean ± SD) between propranolol (80.8 ± 0.3%; 95% confidence interval [CI], 80.7-81.0) and vehicle (81.1 ± 0.6%; 95% CI, 80.8-81.4) (p = 0.668) or between propranolol/clonidine (80.8 ± 0.3%; 95% CI, 80.7-81.0) and vehicle (p = 0.555). We found no effect of propranolol and propranolol/clonidine on blood-brain barrier permeability and animal motor scores. Unexpectedly, propranolol and propranolol/clonidine caused an increase in epinephrine and syndecan-1 levels.

CONCLUSION: This study does not provide any support for unselective beta-blockade with propranolol or the combination of propranolol and the alfa2-agonist clonidine on brain water content. The novel finding of an increase in plasma concentrations of epinephrine and syndecan-1 after propranolol treatment in traumatic brain injury is of unclear significance and should be investigated further.

Original languageEnglish
JournalThe Journal of Trauma and Acute Care Surgery
Volume84
Issue number1
Pages (from-to)89-96
ISSN0022-5282
DOIs
Publication statusPublished - 2018

    Research areas

  • Adrenergic alpha-2 Receptor Agonists/pharmacology, Adrenergic beta-Antagonists/pharmacology, Animals, Blood-Brain Barrier/drug effects, Brain Edema/etiology, Brain Injuries, Traumatic/complications, Capillary Permeability/drug effects, Clonidine/pharmacology, Disease Models, Animal, Glycocalyx/drug effects, Male, Propranolol/pharmacology, Rats, Rats, Sprague-Dawley

ID: 215786155