Doxycycline alleviates acute traumatic brain injury by suppressing neuroinflammation and apoptosis in a mouse model

J Neuroimmunol. 2021 Oct 15:359:577672. doi: 10.1016/j.jneuroim.2021.577672. Epub 2021 Jul 24.

Abstract

Traumatic brain injury (TBI) is one of the significant causes of death among young people worldwide. Doxycycline (DOX), an antibiotic with anti-inflammatory effects, has not been used as a therapeutic agent to modify the inflammatory response after the traumatic brain injury. In this study, intraperitoneal administration of DOX reduced significantly the acute inflammatory markers like IL-6 and CD3, microglial migration to the damaged area marked with Iba-1, and neuronal apoptosis assessed with TUNEL assay at 72 h after the trauma. The low dose, 10 mg/kg of DOX had a dominant anti-inflammatory effect; while the high dose, 100 mg/kg of DOX, was more effective in decreasing neuronal apoptosis. In early hours after the head trauma, use of a low dose (10 mg/kg) of DOX for decreasing the acute form of inflammation followed by a high dose (100 mg/kg) for the anti-apoptotic effects particularly in severe head traumas, would be a promising approach to alleviate the brain injury.

Keywords: Doxycycline; Microglia; Neuroinflammation; Traumatic brain injury.

MeSH terms

  • Animals
  • Apoptosis / drug effects*
  • Apoptosis / physiology
  • Brain Injuries, Traumatic / drug therapy*
  • Brain Injuries, Traumatic / metabolism*
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Doxycycline / pharmacology
  • Doxycycline / therapeutic use*
  • Inflammation Mediators / antagonists & inhibitors*
  • Inflammation Mediators / metabolism*
  • Male
  • Mice

Substances

  • Inflammation Mediators
  • Doxycycline