Summary: The effects of magnesium, an endogenous in hibitor of calcium entry into neurons, upon ischemic brain damage were investigated using a well-character ized model of focal cerebral ischemia in rats. Infarct vol umes were determined by 2,3,5-triphenyltetrazolium chloride transcardiac perfusion 48 h after middle cerebral artery (MCA) occlusion. The area of ischemic damage was quantified by image analysis in coronal sections taken every 0.5 mm. MgCI2 (l mmol/kg) was injected inMagnesium plays an essential role in cellular physiology. It is involved in the activation of � 300 enzymes, including those catalyzing energy producing and energy-consuming reactions (Ebel and Gunther, 1980). In the extracellular space, mag nesium competes with calcium to reduce calcium entry into cells (Altura and Altura, 1981), blocks both voltage-sensitive and N-methyl-D-aspartate (NMDA)-activated channels (Iseri and French, 1984; Nowak et aI. , 1984), is implicated in the reg ulation of cerebral vascular tone (Seelig et aI. , 1983), and inhibits the release of excitatory amino acids (Rothman, 1984). These properties make mag nesium an excellent candidate for preventing brain damage.There is evidence that the neuronal death that follows cerebral ischemia may be due to a massive release of excitatory amino acids, particularly glu tamate (Rothman and Olney, 1986). Most studies suggest that a calcium influx into neurons is a cru cial step of the deleterious cascade triggered by Received March [5, 199[; revised April 29, 1991 ischemia (Schanne et aI. , 1979; Siesj6 and Bengts son, 1989). Several studies have demonstrated that magnesium can protect against anoxic damage in vitro (Ames and Nesbett, 1983;Rothman, 1983; Kass et aI. , 1988) and against applied glutamate (Gibson and Reif-Lehrer, 1985). Treatment with magnesium has also been shown to limit damage and improve outcome after global cerebral ischemia (Tsuda et aI. , 1989), brain trauma (Vink et aI. , 1988McIntosh et aI. , 1989), and spinal cord ischemia (Vacanti and Ames, 1984; Robertson et aI. , 1986).We have therefore investigated whether treat ment with MgCl 2 can reduce infarct volume in rats following focal cerebral ischemia. Intracranial oc clusion of the middle cerebral artery (MCA) in rats has been chosen because it results in highly repro ducible lesions. There is good evidence that this model is most pertinent in terms of pharmacological therapy of stroke (MacKenzie et aI. , 1986). The ef fects of administering a combination of MgCl 2 and insulin were also investigated so as to minimize any influence of magnesium-induced hyperglycemia.
MATERIALS AND METHODSThe experiments were performed on 61 male Fischer-344 rats weighing 280-310 g. The rats had free access to food and water prior to experimentation.
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Induction of focal ischemiaThe rats were anesthetized with halothane (1.5%) in oxygen. Rectal temperature was measured and main tained within the normal physiological range during sur gery. Left MCA occlusion was performed by a subtem poral approach,...