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

Genét, Gustav Folmer LU ; Bentzer, Peter LU ; Hansen, Morten Bagge; Ostrowski, Sisse Rye and Johansson, Pär Ingemar (2018) In Journal of Trauma and Acute Care Surgery 84(1). p.89-96
Abstract

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... (More)

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.

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organization
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type
Contribution to journal
publication status
published
subject
keywords
Blood-brain barrier breakdown, brain water content, clonidine, glycocalyx, propranolol
in
Journal of Trauma and Acute Care Surgery
volume
84
issue
1
pages
8 pages
publisher
Lippincott Williams and Wilkins
external identifiers
  • scopus:85040008433
ISSN
2163-0755
DOI
10.1097/TA.0000000000001708
language
English
LU publication?
yes
id
82dbd1b1-9b8a-41cc-8b24-05fe65d9db86
date added to LUP
2018-01-22 10:28:10
date last changed
2018-01-22 10:28:10
@article{82dbd1b1-9b8a-41cc-8b24-05fe65d9db86,
  abstract     = {<p>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 alfa<sub>2</sub>-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 alfa<sub>2</sub>-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.</p>},
  author       = {Genét, Gustav Folmer and Bentzer, Peter and Hansen, Morten Bagge and Ostrowski, Sisse Rye and Johansson, Pär Ingemar},
  issn         = {2163-0755},
  keyword      = {Blood-brain barrier breakdown,brain water content,clonidine,glycocalyx,propranolol},
  language     = {eng},
  number       = {1},
  pages        = {89--96},
  publisher    = {Lippincott Williams and Wilkins},
  series       = {Journal of Trauma and Acute Care Surgery},
  title        = {Effects of propranolol and clonidine on brain edema, blood-brain barrier permeability, and endothelial glycocalyx disruption after fluid percussion brain injury in the rat},
  url          = {http://dx.doi.org/10.1097/TA.0000000000001708},
  volume       = {84},
  year         = {2018},
}