Turner Renee J, Van den Heuvel Corinna, Vink Robert
Department of Pathology, University of Adelaide, Adelaide, SA, Australia.
J Am Coll Nutr. 2004 Oct;23(5):534S-537S. doi: 10.1080/07315724.2004.10719397.
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.
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.
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.
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.
众所周知，创伤性脑损伤（TBI）会降低脑内游离镁（Mg）浓度，且TBI后给予镁盐可恢复脑内Mg浓度并改善功能预后。在存在出血的情况下，给予镁盐会加剧损伤过程并使预后恶化。替代给予镁盐的方法可能是使用氨氯地平预防细胞内Mg流失，氨氯地平可抑制Na(+)/Mg(2+)交换。
在本研究中，成年雄性Sprague-Dawley大鼠采用弥漫性TBI的撞击加速模型致伤，并在伤后30分钟静脉注射100 μmol/kg氨氯地平，或等体积的50%二甲亚砜/生理盐水。
与接受载体治疗的对照组相比，氨氯地平并未改善TBI后的功能预后（运动或认知预后）。组织学检查显示，氨氯地平治疗显著增加了海马体中半胱天冬酶-3的表达（凋亡）、延髓中的轴突肿胀以及皮质中的暗细胞变化程度（细胞应激）。磷核磁共振显示，氨氯地平在损伤后并未增加游离Mg浓度。
因此，创伤后30分钟给予氨氯地平对预防TBI后的Mg流失无效。此外，在TBI相关的Mg下降已经开始后给予氨氯地平，可能会加剧损伤，部分原因是抑制Na(+)/Mg(2+)反向转运并阻止Mg重新进入细胞，还可能是抑制其他与Na(+)相关的转运体。
