Elsevier

Neuroscience

Volume 44, Issue 2, 1991, Pages 335-341
Neuroscience

Mg2+ Administered up to twenty-four hours following reperfusion prevents ischemic damage of the CA1 neurons in the rat hippocampus

https://doi.org/10.1016/0306-4522(91)90058-VGet rights and content

Abstract

Inductively coupled plasma emission spectrometry analysis was applied to determine ischemiainduced 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.

Reference (37)

  • AlpsB.J. et al.

    Comparative protective effects of nicardipine, flunarizine, lidoflazine and nimodipine against ischaemic injury in the hippocampus of the Mongolian gerbil

    Br. J. Pharmac.

    (1988)
  • AscherP. et al.

    The role of divalent cations in theN-methyl-d-aspartate responses of mouse central neurons in culture

    J. Physiol.

    (1988)
  • BakerP.F. et al.

    Mobility and transport of magnesium in squid giant axons

    J. Physiol.

    (1972)
  • BoweryN.G. et al.

    Quantitative autoradiography of [3H]-MK-801 binding sites in mammalian brain

    Br. J. Pharmac.

    (1988)
  • Caldwell-ViolichM. et al.

    Magnesium content and net fluxes in squid giant axons

    J. gen. Physiol.

    (1979)
  • CromptonM. et al.

    A kinetic study of the energy-linked influx of Ca2+ into heart mitochondria

    Eur. J. Biochem.

    (1976)
  • DeshpandeJ.K. et al.

    Calcium accumulation and neuronal damage in the rat hippocampus following cerebral ischemia

    J. cerebr. Blood Flow Metab.

    (1987)
  • FlatmanP.W.

    Magnesium transport across cell membranes

    J. Membrane Biol.

    (1984)
  • Cited by (112)

    • Neuroprotective effect of magnesium supplementation on cerebral ischemic diseases

      2021, Life Sciences
      Citation Excerpt :

      In this study, magnesium chloride was injected into the hippocampus of rats 10 min prior to ischemia or at 0, 2, 12, 24, or 48 h post-ischemia. Magnesium supplementation into the brain parenchyma within 24 h after ischemia can significantly improve neuronal death caused by cerebral ischemia [162]. Another study of magnesium supplementation into the brain parenchyma used magnesium sulfate, infusion of which into the hippocampal CA1 area increased the survival rate of neurons within the area after ischemia [163].

    • Vitamins and nutrients as primary treatments in experimental brain injury: Clinical implications for nutraceutical therapies

      2016, Brain Research
      Citation Excerpt :

      The use of Mg2+ therapies to promote recovery of function has been investigated for several decades. Treatment with magnesium has been used in models of ischemia (Izumi et al., 1991; Tsuda et al., 1991; Vacanti and Ames, 1984), focal cortical lesions (Hoane et al., 2000, 1998, 1997; Hoane and Barth, 2001, 2002), and spinal cord injuries (Kwon et al., 2010) to highlight but a few of many studies. In experimental TBI, previous work has identified that dietary deficiencies in Mg2+ lead to poorer functional outcomes and increased cell death; however, some of these deficits can be rescued by Mg2+ administration and supplementation post injury (Heath and Vink, 1999; Hoane et al., 2008a; McIntosh et al., 1988).

    • A comparative study of treatment for brain edema: Magnesium sulphate versus dexamethasone sodium phosphate

      2008, Journal of Clinical Neuroscience
      Citation Excerpt :

      Magnesium is a well-documented neuroprotective agent in experimental brain and spinal cord injury.7,9 Experimental studies have shown the neuroprotective effect of magnesium treatment after focal and global brain ischemia,6,8,23 traumatic brain injury,9 acute spinal cord contusion7 and subarachnoid hemorrhage.24 Kaptanoglu et al. demonstrated that magnesium sulphate protects the blood-spinal cord barrier, improves clinical recovery, and protects spinal cord ultrastructure in experimental spinal cord injury in rats.7

    View all citing articles on Scopus
    View full text