Traumatic Brain Injury, Calcium Influx, ATP depletion, and Magnesium

This is a great article showing that traumatic brain injuries produce impairments in mitochondrial activity that can be reversed, at least soon after the injury, by reductions in calcium influx (such as with calcium channel blockers or magnesium):

http://www.jnsonline.org/jns/issues/v93n5/pdf/n0930815.pdf

Excessive calcium influx also occurs in smooth muscle cells during vasospasm, and things like magnesium or drug calcium channel blockers (magnesium acts as a calcium channel blocker) are really potent cerebral vasodilators. The smooth muscle cells in cerebral blood vessels, in particular, are very sensitive to excessive calcium influx. The above article is very interesting, and the authors mention that increases in oxygen delivery, such as from thrombolysis and reperfusion/recanalization, can fail to restore ATP levels when calcium influx and the free cytosolic calcium levels are elevated. They also make the interesting point that early after traumatic brain injuries, the calcium influx can be impairing mitochondrial function without producing "structural" changes and damage to mitochondria (without producing irreversible damage). It's only later that the numbers of functional mitochondria decrease or that mitochondrially-mediated apoptosis occurs.

Here's an interesting article, out of countless similar ones, showing that magnesium is drastically depleted from the brain after a stroke and that excessive calcium influx into the cytoplasm, in different cell types, is accompanied by the magnesium depletion, indicating that magnesium depletion contributes to vasospasm. Magnesium has been used to treat vasospasm (many articles) and acts as a physiological calcium channel blocker in many cell types. Here's the stroke article:

http://www.ncbi.nlm.nih.gov/pubmed/9259458

A couple of big mechanisms by which elevations in free cytosolic calcium produce ATP depletion are by activating cytosolic calcium-dependent proteases that lead to all sorts of inflammatory changes in proteins in the cell, producing mitochondrial swelling, and causing ATP depletion through the activation of calcium-dependent ATPases. There are too many articles to cite any one, and it's a similar situation for articles on the use magnesium in treating ischemia and vasospasm. Here's a hastily-done search on the role of calcium-dependent proteases, which is a big mechanism in many cell types and types of disease states, in the detrimental responses to ischemia (almost 29,000 results on google scholar):

http://scholar.google.com/scholar?num=50&hl=en&lr=&safe=off&q=calcium+dependent+proteases+ischemia