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


CONCLUSIONS
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.
Vink
Robert
R
Department of Pathology, University of Adelaide, Adelaide, SA, Australia. Robert.vink@adelaide.edu.au
Donkin
J J
JJ
Cruz
M I
MI
Nimmo
Alan J
AJ
Cernak
Ibolja
I
D000818:Animals; D001930:Brain Injuries / Q000378:metabolism*; D006706:Homeostasis; D008274:Magnesium / Q000378:metabolism*; D008275:Magnesium Deficiency; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D011480:Protease Inhibitors / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013373:Substance P / Q000037:antagonists & inhibitors*; D014364:Tryptophan / Q000031:analogs & derivatives* / Q000494:pharmacology*
D011480:Protease Inhibitors; D013373:Substance P; C006392:N-acetyltryptophan; D014364:Tryptophan; D008274:Magnesium