A substance P antagonist increases brain intracellular free magnesium concentration after diffuse traumatic brain injury in rats.

Abstract

OBJECTIVE:

Magnesium (Mg) deficiency has been shown to increase substance P release and induce a pro-inflammatory response that can be attenuated with the administration of a substance P-antagonist. Neurogenic inflammation has also been implicated in traumatic brain injury (TBI), a condition where brain intracellular free magnesium (Mg(f)) decline is known to occur and has been correlated with functional outcome. We therefore examined whether a substance P antagonist restores brain intracellular free magnesium concentration following TBI.

METHODS:

Male, adult Sprague-Dawley rats were injured using the Cernak impact acceleration model of diffuse TBI. At 30 min after injury, animals were administered either 0.25 mg/kg i.v. n-acetyl tryptophan or equal volume saline. Prior to and 4 h after induction of injury, phosphorus magnetic resonance spectra were acquired using a 7-tesla magnet interfaced with a Bruker console. Mg(f) was calculated from the chemical shift of the beta ATP. Before injury, Mg(f) was 0.51 +/- 0.05 mM (SEM).

RESULTS:

By 4 hr after injury, Mg(f) had significantly declined to 0.27 +/- 0.02 mM in saline treated rats. In contrast, rats treated with n-acetyl tryptophan had a Mg(f) of 0.47 +/- 0.06 mM at 4 h after injury, which was not significantly different from preinjury values. There were no significant differences in pH between the treatment groups.

CONCLUSION:

It seems that any beneficial effect of a substance P antagonist on functional outcome following TBI may be related to improvement in brain Mg homeostasis induced by the compound.

• Authors: Robert Vink, J J Donkin, M I Cruz, Alan J Nimmo, Ibolja Cernak
• Journal: Journal of the American College of Nutrition (J Am Coll Nutr) Vol. 23 Issue 5 Pg. 538S-540S (Oct 2004) ISSN: 0731-5724 [Print] United States
• PMID: 15466960 (Publication Type: Journal Article)

Chemical References

• Protease Inhibitors
• Substance P
• N-acetyltryptophan
• Tryptophan
• Magnesium

Topics

• Animals
• Brain Injuries (metabolism)
• Homeostasis
• Magnesium (metabolism)
• Magnesium Deficiency
• Magnetic Resonance Spectroscopy
• Male
• Protease Inhibitors (pharmacology)
• Rats
• Rats, Sprague-Dawley
• Substance P (antagonists & inhibitors)
• Tryptophan (analogs & derivatives, pharmacology)