Sodium butyrate exerts neuroprotective effects by restoring the blood-brain barrier in traumatic brain injury mice

Brain Res. 2016 Jul 1:1642:70-78. doi: 10.1016/j.brainres.2016.03.031. Epub 2016 Mar 24.

Abstract

Sodium butyrate (SB) has been widely used to treat cerebral diseases. The aim of the present study is to examine the neuroprotective effects of SB on early TBI in mice and to explore the underlying mechanisms of these effects. TBI was induced using a modified weight-drop method. Neurological deficits were evaluated according to the neurological severity score (NSS), brain oedema was measured by brain water content, and blood-brain barrier (BBB) permeability was evaluated by Evans blue (EB) dye extravasation. Neuronal injury was assessed by hematoxylin and eosin (H&E) staining and Fluoro-Jade C staining. The expression of tight junction-associated proteins, such as occludin and zonula occludens-1 (ZO-1), was analysed by western blotting and immunofluorescence. Our results showed that mice subjected to TBI exhibited worsened NSS, brain oedema, neuronal damage and BBB permeability. However, these were all attenuated by SB. Moreover, SB reversed the decrease in occludin and ZO-1 expression induced by TBI. These findings suggest that SB might attenuate neurological deficits, brain oedema, neuronal change and BBB damage, as well as increase occludin and ZO-1 expression in the brain to protect against TBI. The protective effect of SB may be correlated with restoring the BBB following its impairment.

Keywords: Blood-brain barrier; Brain oedema; Neuronal degeneration; Sodium butyrate; Traumatic brain injury.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Behavior, Animal / drug effects
  • Blood-Brain Barrier / drug effects*
  • Blood-Brain Barrier / metabolism
  • Brain Edema / metabolism
  • Brain Injuries, Traumatic / metabolism*
  • Brain Injuries, Traumatic / pathology
  • Brain Injuries, Traumatic / prevention & control
  • Butyric Acid / administration & dosage*
  • Cell Membrane Permeability
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Neurons / drug effects*
  • Neurons / metabolism
  • Neuroprotective Agents / administration & dosage*
  • Occludin / metabolism
  • Zonula Occludens-1 Protein / metabolism

Substances

  • Neuroprotective Agents
  • Occludin
  • Ocln protein, mouse
  • Tjp1 protein, mouse
  • Zonula Occludens-1 Protein
  • Butyric Acid