Apoptotic Change in Response to Magnesium Therapy after Moderate Diffuse Axonal Injury in Rats

ABSTRACT

The biochemical factors related to moderation of secondary or delayed damage to the central nervous system (CNS) remain undefined. We have recently demonstrated that the weight- drop induced moderate diffuse axonal injury (mDAI) in rats causes a rapid decline in serum ionized magnesium (Mg2+) and a significant increase in the amount of serum ionized calcium (Ca2+) relative to Mg2+ (Ca2+/ Mg2+). For three hours, serum Mg2+ levels remained significantly depressed at 76% of preinjury values (p 0.05). Head trauma resulted in a small decrease of Ca2+ (about 10%), but a significant increase in the amount of Ca2+/Mg2+ (mean value in control group in injured group for 3 hours after trauma =4.65 +/-0.012 5.69 +/-0.015, p< 0.05) was observed. In order to further investigate the relationship between Mg2+ and brain injury, the effect of Mg2+ treatment on posttraumatic histological changes (apoptotic changes) was examined following the weight-drop induced brain injury. At 30 min postinjury, animals treated with MgSO4 (750micro Ml/kg) showed significant improvements of apoptotic changes when compared to the control group (54.8 +/- 1.7, 51.5 +/- 3.2 at 12, 24 h in control group, 24.8 +/- 2.6, 20.5 +/- 1.4 at 12, 24 h in treated group, p< 0.05). The early decline in serum Mg2+ and the increase in the amount of Ca2+/Mg2+ immediately following brain trauma uncovered by these findings suggest that they may be a critical factor in the development of irreversible tissue injury. If this proves to be the case, treatment with MgSO4 may be effective in improving histological findings following experimental traumatic brain injury in rats.