While brain free
magnesium levels have been shown to decline in a number of acute and chronic brain pathologies, the mechanisms of such decline and the potential for
magnesium administration as a therapeutic intervention are still unclear. In
acute brain injury,
magnesium therapy has failed in recent clinical trials of
trauma, presumably because of an intact blood brain barrier at the time of administration reducing central penetration. Under such conditions,
magnesium's peripheral effects on cardiovascular parameters may dominate over the central, and potentially
neuroprotective, effects of the compound. In contrast,
magnesium has been demonstrated to be beneficial in
lacunar strokes, albeit that recent animal studies indicate that this effect is without any significant reduction of lesion size. Postnatal
magnesium has also been shown to improve neurological outcome in term neonates with perinatal
asphyxia, although this may be limited to cases of mild to moderate
brain injury; no effect is observed following severe
brain injury. Prenatal
magnesium has been reported to be beneficial for outcome in very preterm infants, although this may only be at low doses. Combination
therapies are also showing promise in experimental studies, with combined
magnesium and mild
hypothermia as well as
magnesium and
polyethylene glycol proving effective in
ischemic stroke and in
spinal cord injury, respectively. With respect to
chronic brain injury, recent results indicate that
magnesium deficient mice are susceptible to developing
Parkinson's disease, which is consistent with earlier findings that
magnesium deficiency over a number of generations is associated with the development of
Parkinson's disease. The latter was associated with the appearance of variants of the TRPM channels. Our recent studies have shown that
Parkinson's disease is associated with reduced TRPM2 and TRPM7 channel
mRNA expression. Taken together, a more complete picture is emerging of the role of
magnesium in
brain injury, its therapeutic potential as well the mechanisms associated with its decline.