Effects of Magnesium Administration on Brain Edema and Blood–Brain Barrier Breakdown After Experimental Traumatic Brain Injury in Rats

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Abstract
In this study, we examined the effects of magnesium sulfate administration on brain edema and blood-brain barrier breakdown after experimental traumatic brain injury in rats. Seventy-one adult male Sprague-Dawley rats were anesthetized, and experimental closed head trauma was induced by allowing a 450-g weight to fall from a 2-m height onto a metallic disk fixed to the intact skull. Sixty-eight surviving rats were randomly assigned to receive an intraperitoneal bolus of either 750 micromol/kg magnesium sulfate (group 4; n = 30) or 1 mL of saline (group 2; n = 30) 30 minutes after induction of traumatic brain injury; 39 nontraumatized animals received saline (group 1; n = 21) or magnesium sulfate (group 3; n = 18) with an identical protocol of administration. Brain water content and brain tissue specific gravity, as indicators of brain edema, were measured 24 hours after traumatic brain injury. Blood-brain barrier integrity was evaluated quantitatively 24 hours after injury by spectrophotometric assay of Evans blue dye extravasations. In the magnesium-treated injured group, brain water content was significantly reduced (left hemisphere: group 2, 83.2 +/- 0.8; group 4, 78.4 +/- 0.7 [P <.05]; right hemisphere: group 2, 83.1 +/- 0.7; group 4, 78.4 +/- 0.5. [P <.05]) and brain tissue specific gravity was significantly increased (left hemisphere: group 2, 1.0391 +/- 0.0008; group 4, 1.0437 +/- 0.001 [P <.05]; right hemisphere, group 2, 1.0384 +/- 0.001; group 4, 1.0442 +/- 0.005 [P <.05]) compared with the saline-treated injured group. Evans blue dye content in the brain tissue was significantly decreased in the magnesium-treated injured group (left hemisphere: group 2, 0.0204 +/- 0.03; group 4, 0.0013 +/- 0.0002 [P <.05]; right hemisphere: group 2, 0.0064 +/- 0.0009; group 4, 0.0013 +/- 0.0003 [P <.05]) compared with the saline-treated injured group. The findings of the present study support that beneficial effects of magnesium sulfate exist after severe traumatic brain injury in rats. These results also indicate that a blood-brain barrier permeability defect occurs after this model of diffuse traumatic brain injury, and magnesium seems to attenuate this defect.