Neuroprotective effects of magnesium-sulfate on ischemic injury mediated by modulating the release of glutamate and reduced of hyperreperfusion

Kang, Sung Wook; Choi, Seok-Keun; Park, Eunkuk; Chae, Sujin; Choi, Sang‐Jun; Joo, Hyo Jin; Lee, Gi-Ja; Park, Hun-Kuk

doi:10.1016/j.brainres.2010.11.057

Cited by 35 publications

(22 citation statements)

References 31 publications

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“…Previous studies have demonstrated that it is possible to reduce glutamate release during ischaemia/hypoxia by treatment with tiagabine [29], dantrolene [30], nimodipine [31] or magnesium [32]. In principle, the activation of mK ATP channels should result in smaller increases in intracellular Ca 2+ levels and glutamate release during ischaemia.…”

Section: Discussionmentioning

confidence: 99%

The effects of levosimendan on brain metabolism during initial recovery from global transient ischaemia/hypoxia

et al. 2012

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BackroundNeuroprotective strategies after cardiopulmonary resuscitation are currently the focus of experimental and clinical research. Levosimendan has been proposed as a promising drug candidate because of its cardioprotective properties, improved haemodynamic effects in vivo and reduced traumatic brain injury in vitro. The effects of levosimendan on brain metabolism during and after ischaemia/hypoxia are unknown.MethodsTransient cerebral ischaemia/hypoxia was induced in 30 male Wistar rats by bilateral common carotid artery clamping for 15 min and concomitant ventilation with 6% O2 during general anaesthesia with urethane. After 10 min of global ischaemia/hypoxia, the rats were treated with an i.v. bolus of 24 μg kg-1 levosimendan followed by a continuous infusion of 0.2 μg kg-1 min-1. The changes in the energy-related metabolites lactate, the lactate/pyruvate ratio, glucose and glutamate were monitored by microdialysis. In addition, the effects on global haemodynamics, cerebral perfusion and autoregulation, oedema and expression of proinflammatory genes in the neocortex were assessed.ResultsLevosimendan reduced blood pressure during initial reperfusion (72 ± 14 vs. 109 ± 2 mmHg, p = 0.03) and delayed flow maximum by 5 minutes (p = 0.002). Whereas no effects on time course of lactate, glucose, pyruvate and glutamate concentrations in the dialysate could be observed, the lactate/pyruvate ratio during initial reperfusion (144 ± 31 vs. 77 ± 8, p = 0.017) and the glutamate release during 90 minutes of reperfusion (75 ± 19 vs. 24 ± 28 μmol·L-1) were higher in the levosimendan group. The increased expression of IL-6, IL-1ß TNFα and ICAM-1, extend of cerebral edema and cerebral autoregulation was not influenced by levosimendan.ConclusionAlthough levosimendan has neuroprotective actions in vitro and on the spinal cord in vivo and has been shown to cross the blood–brain barrier, the present results showed that levosimendan did not reduce the initial neuronal injury after transient ischaemia/hypoxia.

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Section: Discussionmentioning

confidence: 99%

The effects of levosimendan on brain metabolism during initial recovery from global transient ischaemia/hypoxia

et al. 2012

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“…The mean number of stained cells was determined by three researchers who were blinded to the groups as previously described. 30 Chronic histology. Long-term neuronal survival was assessed on Day 15 post-injury.…”

Section: Histologymentioning

confidence: 99%

MMP-9 Inhibitor SB-3CT Attenuates Behavioral Impairments and Hippocampal Loss after Traumatic Brain Injury in Rat

Feng

Yin

Gao

et al. 2014

Journal of Neurotrauma

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The aim of this study was to evaluate the potential efficacy of SB-3CT, a matrix metallopeptidase 9 inhibitor, on behavioral and histological outcomes after traumatic brain injury (TBI) in rats. Adult male Sprague-Dawley rats were randomly divided into three groups (n = 15/group): TBI with SB-3CT treatment, TBI with saline, and sham injury. The TBI model was induced by a fluid percussion TBI device. SB-3CT (50 mg/kg in 10% dimethyl sulfoxide) was administered intraperitoneally at 30 min, 6 h, and 12 h after the TBI. Motor function (beam-balance/beam-walk tests) and spatial learning/memory (Morris water maze) were assessed on post-operative Days 1 -5 and 11-15, respectively. Fluoro-Jade staining, immunofluorescence, and cresyl violet-staining were carried out for histopathological evaluation at 24 h, 72 h, and 15 days after TBI, respectively. It was shown that TBI can result in significant behavioral deficit induced by acute neurodegeneration, increased expression of cleaved caspase-3, and long-term neuronal loss. SB-3CT intervention via the current regime provides robust behavioral protection and hippocampal neurons preservation from the deleterious effects of TBI. Hence, the efficacy of SB-3CT on TBI prognosis could be ascertained. It is believed that the current study adds to the growing literature in identifying SB-3CT as a potential therapy for human brain injury.

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“…These paradoxical perspectives regarding the neuroprotective effect of MgSO 4 administration could be the consequence of the variability in the study design, depending on the dose and the experimental model, making it difficult to compare the outcomes directly. Studies with newborn rodents and different magnesium doses presented divergent results, including neuroprotection [125,126,127,128,129,130] or its absence [115,131,132,133,134,135]. On the other hand, although lamb or pig models are closer to humans [136], up to date there are few studies on the protective effect of MgSO 4 administration in these newborn mammals suffering neonatal HI encephalopathy [114].…”

Section: Pharmacological Therapiesmentioning

confidence: 99%

Neuroprotective Therapies after Perinatal Hypoxic-Ischemic Brain Injury

et al. 2013

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Hypoxic-ischemic (HI) brain injury is one of the main causes of disabilities in term-born infants. It is the result of a deprivation of oxygen and glucose in the neural tissue. As one of the most important causes of brain damage in the newborn period, the neonatal HI event is a devastating condition that can lead to long-term neurological deficits or even death. The pattern of this injury occurs in two phases, the first one is a primary energy failure related to the HI event and the second phase is an energy failure that takes place some hours later. Injuries that occur in response to these events are often manifested as severe cognitive and motor disturbances over time. Due to difficulties regarding the early diagnosis and treatment of HI injury, there is an increasing need to find effective therapies as new opportunities for the reduction of brain damage and its long term effects. Some of these therapies are focused on prevention of the production of reactive oxygen species, anti-inflammatory effects, anti-apoptotic interventions and in a later stage, the stimulation of neurotrophic properties in the neonatal brain which could be targeted to promote neuronal and oligodendrocyte regeneration.

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Neuroprotective effects of magnesium-sulfate on ischemic injury mediated by modulating the release of glutamate and reduced of hyperreperfusion

Cited by 35 publications

References 31 publications

The effects of levosimendan on brain metabolism during initial recovery from global transient ischaemia/hypoxia

The effects of levosimendan on brain metabolism during initial recovery from global transient ischaemia/hypoxia

MMP-9 Inhibitor SB-3CT Attenuates Behavioral Impairments and Hippocampal Loss after Traumatic Brain Injury in Rat

Neuroprotective Therapies after Perinatal Hypoxic-Ischemic Brain Injury

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