Lee EJ, Ayoub IA, Harris FB, Hassan M, Ogilvy CS, Maynard KIMexiletine and magnesium independently, but not combined, protect against permanent focal cerebral ischemia in Wistar rats. J Neurosci Res 58:442-448
The neuroprotective effect of mexiletine (Mex), a potent Na(+) channel blocker which decreases neuronal energy demands and prevents energy depletion during ischemia, was evaluated in Wistar rats subjected to permanent middle cerebral artery (MCA) occlusion. Postmortem infarct volumes were determined by quantitative image analysis of triphenyltetrazolium (TTC)-stained brain sections. Pretreatment with Mex resulted in a significant infarct volume reduction when administered intraperitoneally, either at the dosage of 50 or 60 mg/kg, 1 hr before MCA occlusion (P < 0.05). Delayed treatment with Mex (50 mg/kg) also had neuroprotective effects when given at 0.5 hr (< 0.05), but not 2-4 hr, after MCA occlusion. Intraarterial administration of MgSO(4) (90 mg/kg), in combination with Mex at 60 mg/kg, showed no additive neuroprotective effect, although each agent independently reduced the MCA occlusion-induced infarction volume (P < 0.05). Our results indicate that a single, acute administration of Mex is neuroprotective against permanent focal cerebral ischemia, but perhaps chronic administration is needed to establish a more effective therapeutic window beyond 0.5 hr. Moreover, the present in vivo data do not favor a combined use of Mg(2+) with Mex for limiting ischemic injury in the brain, since these agents caused cardiopulmonary suppression, which may have led to the loss of the neuroprotective effect of each agent independently.
"With energy depletion, presynaptic reuptake of glutamate is impeded, which further increases the accumulation of glutamate in the extracellular space. Thus, with a consequent influx of Na + and Ca 2+ ions through the channels, N-methyl-D-aspartate (NMDA)-type glutamate receptor, which gate channels for highly permeable Ca 2+ , can rapidly trigger excitotoxicity (Lee et al., 1999). Based on these data and ideas, several NMDA-antagonist drugs were developed and used in human stroke trials to minimize the effects of the ischemic cascade. "
[Show abstract][Hide abstract] ABSTRACT: Ginkgo biloba exerts many pharmacological actions. It possesses antioxidant properties, the ability of neurotransmitter/receptor modulation and antiplatelet activation factor. This research is designed to investigate the neuroprotective effects of long-term treatment with EGb761 (a standard form of the extract of Ginkgo biloba leaf) in combination with MgSO(4), FK506, or MK-801 on the infarct volume of male gerbils' brain induced by unilateral middle cerebral artery occlusion (MCAO). Thirty-five gerbils fed a standard diet were intragastrically given water or EGb761 (100 mg/kg/day) for one week. Five randomized groups were established: control (n = 7), EGb761 (n = 8), EGb761 + MgSO(4) (n = 7), EGb761 + FK506 (n = 7), and EGb761 + MK-801 (n = 6). The three drug-combination groups were injected with MgSO(4) (90 mg/kg), FK506 (0.5 mg/kg), or MK-801 (1 mg/kg), respectively 30 min before MCAO. Gerbils were anesthetized and craniectomized to expose the right middle cerebral artery (MCA). The right MCA was constricted with an 8-0 suture to produce a permanent ligation for 24 hours. Postmortem infarct volumes were determined by quantitative image analysis of 2,3,5-triphenyltetrazolium chloride (TTC)-stained brain sections. Results showed that the total infarct volumes of the four treated groups either EGb761 alone or in combination with drugs were lower than the control group by 36.1% (EGb761 alone), 40.3% (EGb761 + MgSO(4)), 35.3% (EGb761 + FK506), and 56.4% (EGb761 + MK-801), respectively (p < 0.01). The main affected areas of the brain in the four treated groups were significantly focused between 4 and 6 mm from the frontal pole, when compared to the control group (p < 0.01). All animals in the five groups had infarctions in both cortex and subcortex. These results indicate that long-term pre-treatment of EGb761 administered either alone or in combination with drugs significantly effective neuroprotection on infarct volume in gerbil ischemic brains.
The American Journal of Chinese Medicine 01/2006; 34(5):803-17. DOI:10.1142/S0192415X06004302 · 2.76 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Adequate magnesium stores are vitally important for life. Critically ill patients will almost always have diminished levels of circulating magnesium, and this predisposes them to a variety of adverse effects, some life threatening. The causes of hypomagnesemia are many and varied, but in the critically ill, losses from the kidneys, often secondary to medications and from the gastrointestinal (GI) tract, predominate. The measurement of magnesium is not straightforward, although many clinicians are now switching to the use of ionized magnesium from ion selective electrodes. The use of supplemental magnesium in acute flares of asthma has some support in medical literature, especially for those patients with severe disease who fail traditional therapy. Magnesium holds the preeminent position in the treatment of pre-eclampsia and eclampsia in the minds of most obstetricians, who have decades of experience showing it to be both effective and safe. Magnesium is clearly useful for certain types of ventricular tachycardia, and probably assists in the treatment of several types of supraventricular tachycardia. Its role in acute myocardial ischemia is less certain, although there is no benefit once reperfusion therapy has already been carried out. Finally, the role of magnesium in the treatment of acute cerebral insults is an exciting area of active investigation with initial studies suggesting much promise.
Critical Care Clinics 02/2001; 17(1):155-73, viii. DOI:10.1016/S0749-0704(05)70157-3 · 2.16 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: In this study it is hypothesized that magnesium sulphate in asphyxiated full-term neonates could lead to a gradual improvement in background pattern of the amplitude integrated EEG (aEEG), an early marker of hypoxic-ischaemic brain injury. In a double-blind, randomized, controlled pilot study of 22 asphyxiated full-term neonates 8 received magnesium sulphate, reaching serum Mg2+ levels of 2.5 mmol/L. Magnesium sulphate had no immediate effect on aEEG-patterns. At 12 h of age, aEEG was more depressed compared with aEEG at 3 h in 6 of the 8 magnesium-treated neonates, and in 3 of the 14 placebo-treated neonates (Mg2+ vs placebo: p < 0.05, Mann-Whitney). No further significant changes in aEEG were seen between 12 and 24 h. Outcome was unfavourable in 4 of the 8 magnesium-treated neonates, and in 8 of the 14 placebo-treated neonates. Conclusion: Magnesium sulphate did not have a positive effect on aEEG patterns in this small group of asphyxiated term neonates.
Celine S Gathier, Jan Willem Dankbaar, Mathieu van der Jagt, Bon H Verweij, Annemarie W Oldenbeuving, Gabriel J E Rinkel, Walter M van den Bergh, Arjen J C Slooter
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