Amiloride increases neuronal damage after traumatic brain injury in rats.

Abstract

OBJECTIVE:

It is well known that traumatic brain injury (TBI) decreases brain free magnesium (Mg) concentration, and that administration of Mg salts after TBI restores concentration of Mg in brain and improves functional outcome. In the presence of hemorrhage, administration of Mg salts exacerbates the injury process and worsens outcome. An alternative to administration of Mg salts may be to prevent cellular loss of Mg with use of amiloride, which inhibits the Na(+)/Mg(2+) exchange.

METHODS:

In the present study, male, adult Sprague-Dawley rats were injured using the impact acceleration model of diffuse TBI and administered either 100 mols/kg i.v. amiloride, or an equal volume of 50% DMSO/saline, 30 minutes (min) after injury.

RESULTS:

Amiloride did not improve functional outcome (motor or cognitive outcome) after TBI relative to vehicle treated controls. Histologically, treatment with amiloride significantly increased hippocampal caspase-3 expression (apoptosis), axonal swellings in the medulla and the degree of dark cell change (cell stress) in the cortex. Phosphorus NMR demonstrated that amiloride did not increase free Mg concentration after injury.

CONCLUSIONS:

Thus, amiloride is ineffective in preventing Mg loss after TBI when administered 30 min after trauma. Moreover, by administering amiloride after the TBI-related Mg decline has already been initiated, it may exacerbate injury by, in part by inhibiting Na(+)/Mg(2+) antiport and preventing entry of Mg back into the cell, and also by inhibiting other Na(+) linked transporters.

• Authors: Renee J Turner, Corinna Van den Heuvel, Robert Vink
• Journal: Journal of the American College of Nutrition (J Am Coll Nutr) Vol. 23 Issue 5 Pg. 534S-537S (Oct 2004) ISSN: 0731-5724 [Print] United States
• PMID: 15466959 (Publication Type: Journal Article)

Chemical References

• Diuretics
• Amiloride
• Magnesium

Topics

• Amiloride (pharmacology)
• Animals
• Apoptosis (drug effects)
• Brain (metabolism)
• Brain Injuries (metabolism)
• Cognition (drug effects)
• Diuretics (pharmacology)
• Magnesium (metabolism)
• Male
• Motor Activity (drug effects)
• Rats
• Rats, Sprague-Dawley