Effects of propranolol and clonidine on brain edema, blood-brain barrier permeability, and endothelial glycocalyx disruption after fluid percussion brain injury in the rat
Research output: Contribution to journal › Journal article › peer-review
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 language | English |
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Journal | The Journal of Trauma and Acute Care Surgery |
Volume | 84 |
Issue number | 1 |
Pages (from-to) | 89-96 |
ISSN | 0022-5282 |
DOIs | |
Publication status | Published - 2018 |
- 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
Research areas
ID: 215786155