The effect of Magnesium, Memantine and combination of Magnesium and Memantine on Blood Brain Barrier Permeability and Brain Oedema after Experimental Traumatic Diffuse Brain Injury

Abstract

Objective: It has been shown that excess amount of glutamate released after primary neuronal injury by head trauma causes secondary injuries in the adult brain. Aiming to prevent this secondary injury a wide range of N-Methyl-D-aspartate receptor antagonist drugs have been investigated in experimental studies. Magnesium sulphate and memantine are pharmacological agents widely used clinically for this specific indication; prevention of secondary neural injury. According to current literature although these two drugs have been used alone or in combination with different drugs, they have not been tried together in combination before. This experimental study is aimed to investigate the effect of magnesium, memantine and the combination of two agents on the permeability of blood brain barrier (BBB) and the quantity of diffuse cerebral oedema after experimentally induced traumatic brain injury.

Methods: A standard traumatic brain injury was induced in Sprague-Dawley rats by a controlled impact device using a mass free falling from a certain height. Animals were introduced one of the following drugs of the same amount, intraperitoneally 30 minutes after traumatic brain injury; saline (1 ml/kg), magnesium sulphate (270 mg/kg), memantine (10 mg/kg), and magnesium sulphate plus memantine (270 mg/kg+10 mg/kg). To determine the brain oedema, the specific gravity of the injured brain tissue was evaluated. The changes in permeability of the BBB were investigated by Evans Blue dye that is known to bind to serum albumin.

Results: In treatment groups, the specific gravity values significantly increased when compared with the control group. Evans blue dye content in the brain tissue was significantly reduced with respect to the control group.

Conclusion: In preventing the secondary insult occurring after traumatic brain injury, NMDA receptor antagonists: Magnesium sulphate, memantine and combination of magnesium sulphate and memantine are shown to be effective by decreasing diffuse cerebral oedema and restoring the BBB.