Effect of magnesium, MK-801 and combination of magnesium and MK-801 on blood-brain barrier permeability and brain edema after experimental traumatic diffuse brain injury

Neurol Res. 2009 Nov;31(9):977-81. doi: 10.1179/174313209X385617. Epub 2009 Feb 11.

Abstract

Objective: Glutamate antagonists are very attractive drugs in laboratory works to protect neural tissue against ischemia. In this work, the effects of magnesium, MK-801 and combination of magnesium and MK-801 on blood-brain barrier (BBB) and brain edema after experimentally induced traumatic brain injury are evaluated.

Methods: A standard closed head injury was induced on the rats by a controlled impact device using a 450-g free falling mass from a height of 2 m onto a metallic disc fixed to the intact skull. One of the following was injected to animals intraperitoneally 30 minutes after injury: saline, magnesium, MK-801 and magnesium plus MK-801. To quantify the brain edema, the specific gravity of the brain tissue was determined. To demonstrate the alteration of the BBB permeability, Evans blue dye was used as a tracer.

Results: In all treatment groups, the specific gravity of brain tissue values was significantly higher compared with the control group. Evans blue dye content in the brain tissue was significantly reduced in all three treatment groups with respect to the control group. There was no significant difference of effect between the groups of magnesium alone and MK-801 alone when compared with each other and when compared with their combination.

Conclusion: The present data demonstrate that treatment with magnesium, MK-801 and combination of magnesium and MK-801 can reduce formation of brain edema and can help restore BBB permeability after experimental diffuse brain injury.

MeSH terms

  • Animals
  • Blood-Brain Barrier / drug effects*
  • Blood-Brain Barrier / physiopathology
  • Body Water / drug effects
  • Body Water / physiology
  • Brain Edema / drug therapy*
  • Brain Edema / etiology
  • Brain Edema / physiopathology
  • Brain Injuries / complications
  • Brain Injuries / drug therapy*
  • Brain Injuries / physiopathology
  • Diffuse Axonal Injury / complications
  • Diffuse Axonal Injury / drug therapy*
  • Diffuse Axonal Injury / physiopathology
  • Disease Models, Animal
  • Dizocilpine Maleate / pharmacology*
  • Dizocilpine Maleate / therapeutic use
  • Drug Combinations
  • Drug Synergism
  • Evans Blue / pharmacokinetics
  • Head Injuries, Closed / complications
  • Head Injuries, Closed / physiopathology
  • Indicators and Reagents / pharmacokinetics
  • Magnesium Compounds / pharmacology*
  • Magnesium Compounds / therapeutic use
  • Male
  • Neuroprotective Agents / pharmacology
  • Neuroprotective Agents / therapeutic use
  • Rats
  • Rats, Sprague-Dawley
  • Specific Gravity / drug effects
  • Treatment Outcome

Substances

  • Drug Combinations
  • Indicators and Reagents
  • Magnesium Compounds
  • Neuroprotective Agents
  • Evans Blue
  • Dizocilpine Maleate