Effects of propranolol and clonidine on brain edema, blood-brain barrier permeability, and endothelial glycocalyx disruption after fluid percussion brain injury in the rat
(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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- author
- Genét, Gustav Folmer LU ; Bentzer, Peter LU ; Hansen, Morten Bagge ; Ostrowski, Sisse Rye and Johansson, Pär Ingemar
- organization
- publishing date
- 2018
- 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 & Wilkins
- external identifiers
-
- scopus:85040008433
- pmid:28930945
- 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
- 2024-01-14 13:13:06
@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}}, keywords = {{Blood-brain barrier breakdown; brain water content; clonidine; glycocalyx; propranolol}}, language = {{eng}}, number = {{1}}, pages = {{89--96}}, publisher = {{Lippincott Williams & 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}}, doi = {{10.1097/TA.0000000000001708}}, volume = {{84}}, year = {{2018}}, }