Calcium, hypercalcemia, magnesium, and brain ischemia

Calcium is an important constituent of many organs of the body, especially bones and teeth. Normal calcium and magnesium ion concentrations are crucial for the maintenance of homeostasis and cellular function. Calcium is an important mediator of striatal and smooth muscle contraction, and is integral in many coagulation and other blood reactions. The concentration of ionized calcium is normally much higher in the extracellular spaces than within cells. Excessive entry of calcium into cells promotes cell death (Choi, 1995; Lee et al., 1999; Orrenius et al., 1992; Siesjo, 1991; Siesjo and Bengtson, 1989). Hypercalcemia is a relatively common biochemical abnormality that is often caused by hyperparathyroidism but may also be related to a number of pathological entities that include cancer, bone metastases, sarcoidosis, and other conditions. Calcium has become recognized as a key mediator of cell death in cerebrovascular pathophysiology (Lee et al., 1999). As a result, calcium channel antagonists (CCAs) have been tested as neuroprotective agents for the treatment of acute stroke (Horn and Limburg, 2001; Mohr et al., 1994), as well as to mitigate vascular and neuronal effects of vasospasm after subarachnoid hemorrhage (Allen et al., 1983; Haley et al., 1994b; Rinkel et al., 2005; Shibuya et al., 1992). Reviews of the neurological manifestations of hypercalcemia rarely discuss stroke, although such has been reported (Gorelick and Caplan, 1985). Magnesium is another important metallic ion that sometimes functions in a reciprocal way to calcium, a so-called natural calcium antagonist.