Magnesium and Cobalt, not Nimodipine, Protect Neurons Against Anoxic Damage in the Rat Hippocampal Slice

Investigational Therapies for Ischemic Stroke: Neuroprotection and Neurorecovery

“…There is extensive experience with magnesium use, largely in pre-eclampsia/eclampsia, which confirms its safety and tolerability. There are a number of potential mechanisms by which magnesium may act, including increased regional blood flow to ischemic brain areas [71], nonspecific antagonism of all subtypes of voltagesensitive calcium channel [72], noncompetitive blockade of the N-methyl-D-aspartate acid subclass of glutamate receptor [73][74][75][76][77][78], presynaptic glutamate release inhibition [79][80][81][82], potentiation of adenosine action, enhanced recovery of cellular energy metabolism after ischemia [83,84], and improved mitochondrial calcium buffering [85]. The neuroprotective effects of magnesium have been found in many models of ischemic cerebral damage [86][87][88].…”

Brain protection: physiological and pharmacological considerations. Part II: the pharmacology of brain protection

“…In this manner, it was possible to determine if a particular agent impataed any neuroprotective effect solely on the basis of blocking Ca ++ influx into neurons. 65 The authors found that treatment with either magnesium (10 mM) or cobalt (2 mM) imparted protection to the neurons of the hippocampus, an area selectively vulnerable to ischaemia. This protective effect was manifested as an increased recovery of neuronal transmission after the hippocampal slice had been exposed to anoxic conditions, and when compared to the untreated control group.…”

“…In contrast, the authors were unable to observe any protective effect of nimodipine treatment. 65 In addition to examining the hippocampal slice for recovery of neuronal transmission, Kass et al also examined what effect Mg + § and nimodipine had on the ATP depletion that occurs as a result of ischaemia. 65 It has been demonstrated that recovery of electrophysiological activity after anoxia is correlated with the degree of ATP depletion.…”

“…66 Magnesium, but not nimodipine, was found to reduce this depletion of ATP during anoxia which parallels what was observed in regards to their relative contributions to electrophysiologic recovery of the evoked response (neuronal transmission) following anoxia. 65 The differential neuroprotective effects delivered by these Ca § § channel antagonists can be explained in terms of their relative Ca ++ channel sensitivity. At least three types of voltage-sensitive Ca + § channels have been identified (T, N and L) based on their relative sensitivity to blockade by various calcium entry blocking agents (e.g., dihydropyridines), cadmium, a marine snail venom, and inactivation at various voltages.…”

“…66 This maintenance is achieved through the blockade of presynaptic Ca ++ channels and subsequent blockade of neurotransmitter release, and/or blockade of an NMDAglutamate receptor channel which is located postsynaptically. 65 It is presumed that the blockade of Ca ++ channels in both cases leads to a reduction in neural transmission and thus activity of the post-synaptic neurons. Consequently, sodium and calcium influx as a result of neural transmission is reduced significantly and the cellular energy required to reestablish resting ion distribution is reduced as a result.…”