HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Figures Only Full Text Full Text (PDF) Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Vink, R. Articles by Cernak, I. Search for Related Content PubMed PubMed Citation Articles by Vink, R. Articles by Cernak, I.

A Substance P Antagonist Increases Brain Intracellular Free Magnesium Concentration after Diffuse Traumatic Brain Injury in Rats

Department of Pathology, University of Adelaide, Adelaide SA (R.V., J.J.D.), AUSTRALIA
School of Pharmacy and Molecular Sciences, James Cook University, Townsville QLD (A.J.N., I.C.), AUSTRALIA
Department of Neuroscience, Georgetown University, Washington DC (M.I.C.)

Address reprint requests to: Robert Vink, PhD, Department of Pathology, University of Adelaide, Adelaide SA, AUSTRALIA. E-mail: Robert.vink{at}adelaide.edu.au

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.

Key words: brain trauma, brain Mg, inflammation, functional outcome, rats, substance P-antagonist