Propranolol protects cerebral autoregulation and reduces hippocampal neuronal cell death through inhibition of interleukin-6 upregulation after traumatic brain injury in pigs

Br J Anaesth. 2019 Nov;123(5):610-617. doi: 10.1016/j.bja.2019.07.017. Epub 2019 Sep 18.


Background: Traumatic brain injury (TBI) is associated with reduced cerebral blood flow and impaired autoregulation after TBI, which may lead to poor outcome. Clinical evidence has implicated neurological injuries and associated neuroinflammation as causes of cardiac dysfunction. Studies on newborn pigs show an association of elevated catecholamines with a sex-dependent impairment of cerebral autoregulation after TBI. One strategy to decrease sympathetic hyperactivity is pharmacological intervention with beta blockade. We tested the hypothesis that propranolol would prevent the impairment of cerebral autoregulation and tissue changes after TBI via inhibition of interleukin-6 (IL-6) upregulation.

Methods: Using newborn pigs of both sexes equipped with a closed cranial window, TBI was induced via lateral fluid percussion injury. Propranolol was administered at 1 h post-TBI. Analyses included cerebral autoregulation (pial artery reactivity) before and 4 h post-TBI, CSF IL-6 analysed (enzyme-linked immunosorbent assay), and histopathology at 4 h post-TBI.

Results: Propranolol administration prevented impairment of hypotensive dilation in both male and female newborn pigs after fluid percussion injury, which was paralleled by reduced upregulation of IL-6 in the CSF. Moreover, propranolol prevented neuronal cell death in cornu amonis (CA)1 and CA3 hippocampus equivalently in male and female pigs after TBI. Papaverine-induced dilation was unchanged by TBI and propranolol.

Conclusions: These data indicate that sympathetic hyperactivity noted after TBI can be limited by propranolol administration to result in improved brain outcome post-injury via block of IL-6 upregulation, and this effect is irrespective of sex.

Keywords: beta blockers; catecholamine; cerebral autoregulation; histopathology; interleukin-6; neuroinflammation; propranolol; traumatic brain injury.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adrenergic beta-Antagonists / pharmacology
  • Animals
  • Animals, Newborn
  • Brain Injuries, Traumatic / drug therapy*
  • Brain Injuries, Traumatic / pathology
  • Brain Injuries, Traumatic / physiopathology
  • Cell Death / drug effects*
  • Disease Models, Animal
  • Female
  • Hippocampus / drug effects*
  • Hippocampus / physiology
  • Homeostasis / drug effects*
  • Homeostasis / physiology
  • Interleukin-6 / antagonists & inhibitors*
  • Male
  • Neurons / drug effects
  • Propranolol / pharmacology*
  • Swine
  • Up-Regulation / drug effects


  • Adrenergic beta-Antagonists
  • Interleukin-6
  • Propranolol