Mg2+ administered up to twenty-four hours following reperfusion prevents ischemic damage of the Ca1 neurons in the rat hippocampus.
Inductively coupled plasma emission spectrometry analysis was applied to determine ischemia-induced changes of Mg2+ and Ca2+ in vulnerable regions of rat brain. This method can provide an accurate quantification and lower detection limits, as compared to atomic absorption spectrophotometry or several other methods. In the hippocampus, Mg2+ content significantly increases 24 h following 20 min of ischemia, followed by a gradual decrease between 48 and 72 h. Ca2+ accumulation was found at 48 and 72 h. At the cell membrane, Mg2+ plays a role as an endogenous calcium channel blocker of both the receptor-operated and voltage-dependent gates and, in the mitochondria, Mg2+ inhibits Ca2+ uptake processes. We propose that the mobilization of Mg2+ after 24 h reperfusion may counteract the process of ischemia-induced neuronal damage and that decreases of Mg2+ may be correlated with the degree of brain injury. However, in the natural concentration of Mg2+, the counteraction may not be sufficient for a neuroprotective effect. Therefore, after 24 h reperfusion, an artificial enhancement of Mg2+ is necessary for neuroprotection. In order to test the above hypothesis, MgCl2, (50 mM) was administered directly to the CA1 sector of the rat hippocampus before and at various intervals following 20 min of ischemia. Pyramidal cells were evaluated seven days later and neuronal density was determined. Consistent with the hypothesis, a neuroprotective effect was observed, even when MgCl2 was administered 24 h, but not 48 h, after the ischemic episode.
Tsuda
T
T
Department of Neurology, Institute of Brain Disease, Sendai, Japan.
Kogure
K
K
Nishioka
K
K
Watanabe
T
T
D000818:Animals; D001921:Brain / Q000378:metabolism; D002545:Brain Ischemia / Q000473:pathology*; D002118:Calcium / Q000378:metabolism; D002560:Cerebrovascular Circulation; D006624:Hippocampus / Q000473:pathology*; D008274:Magnesium / Q000378:metabolism / Q000494:pharmacology*; D008297:Male; D009474:Neurons / Q000473:pathology*; D051381:Rats; D011919:Rats, Inbred Strains; D015424:Reperfusion; D013997:Time Factors; D014018:Tissue Distribution
D008274:Magnesium; D002118:Calcium