Anxiolytic effect of chronic intake of supplemental magnesium chloride in rat.

Evidence suggest that magnesium dietary supplementation has several health benefits including lowering blood pressure, reducing insulin resistance, and improving symptoms of depression, anxiety, and migraine. Here, we aimed to study the effect of chronic magnesium supplementation on anxiety-like behavior in rats by supplementing with magnesium their drinking water for 30 days. Anxiety-like behavior was induced by subcutaneous injection of veratrin 30 min before performing elevated plus maze and open field tests to measure anxiety levels and locomotion, respectively. We quantify the concentration of magnesium in plasma and cerebrospinal fluid. We used diazepam to compare the efficacy of magnesium supplementation as an anxiolytic agent. Our results show that rats supplemented with magnesium had a statistically significant decrease in anxiety levels with not effects on locomotion and a statistically significant increase in concentration of magnesium in plasma and cerebrospinal fluid. However, the anxiolytic effect of magnesium supplementation washes-out in 12 days. We discuss the advantages of using supplemental magnesium as anxiolytic.

Multicollector Inductively Coupled Plasma-Mass Spectrometry with 1013 Ω Faraday Cup Amplifiers for Ultrasensitive Mg Isotopic Analysis of Cerebrospinal Fluid Microsamples.

Magnesium isotopic analysis of cerebrospinal fluid (CSF) is a potentially interesting approach for studies on neurodegeneration. However, this type of analysis is challenging because of the invasiveness of the sampling and small sample volume. In this work, a novel analytical method was developed for ultrasensitive Mg isotopic analysis of CSF microsamples via multicollector inductively coupled plasma-mass spectrometry (MC-ICP-MS) using high-gain 1013 Ω Faraday cup amplifiers. The intermediate and internal errors on the δ26Mg value were improved up to fourfold using 1013 Ω resistors for the monitoring of both the 24Mg and 26Mg isotopes and up to twofold using a 1011 Ω resistor for the most abundant 24Mg isotope and a 1013 Ω resistor for the 26Mg isotope. Magnesium isotope ratios measured at a concentration level of 7-10 µg L-1 were in good agreement with those obtained using the conventional method at a concentration level of 150 µg L-1. The expanded uncertainty for the quality control CSF material obtained at the ultratrace level was ±0.16‰. Ultrasensitive Mg isotopic analysis was carried out for CSF from hydrocephalus patients using only 5 µL of sample. δMg values thus obtained were not significantly different from those obtained using the conventional method using a sample volume of 400 µL instead (p ≤ 0.05). The Mg isotopic composition of the CSF from hydrocephalus patients ranged between -0.65 and 0.30‰, with a mean δ26Mg value of -0.14 ± 0.27‰.

Short-term effects of early initiation of magnesium infusion combined with cooling after hypoxia-ischemia in term piglets.

BACKGROUND: Neuroprotection from therapeutic hypothermia (HT) is incomplete, therefore additional strategies are necessary to improve long-term outcomes. We assessed the neuroprotective efficacy of magnesium sulfate (MgSO4) bolus and infusion over 48 h plus HT in a piglet model of term neonatal encephalopathy (NE). METHODS: Fifteen newborn piglets were randomized following hypoxia-ischemia (HI) to: (i) MgSO4 180 mg/kg bolus and 8 mg/kg/h infusion with HT (Mg+HT) or (ii) HT and saline 0.5 ml/h (HT). Treatments were initiated 1 h post-HI; HT administered for 12 h (33.5 °C). HI was performed by transient carotid occlusion and inhalation of 6% O2 for 20-25 min. Primary outcomes included aEEG, magnetic resonance spectroscopy (MRS) at 24, and 48 h, and immunohistochemistry. RESULTS: MgSO4 bolus and infusion was well tolerated (no hypotension) and doubled serum magnesium (0.72 vs 1.52 mmol/L) with modest (16%) rise in CSF. In Mg+HT compared to HT, there was overall reduced cell death (p = 0.01) and increased oligodendrocytes (p = 0.002). No improvement was seen on aEEG recovery (p = 0.084) or MRS (Lac/NAA; PCr/Pi; NTP/epp) (p > 0.05) at 48 h. CONCLUSION: Doubling serum magnesium with HT was safe; however, the small incremental benefit of Mg+HT compared to HT is unlikely to translate into substantive long-term improvement. Such an incremental effect might justify further study of MgSO4 in combination with multiple therapies.

Differences in Sampling Site on Postmortem Cerebrospinal Fluid Biochemistry: A Preliminary Study.

Cerebrospinal fluid (CSF) is often analyzed at postmortem. The presented preliminary study compared postmortem CSF samples for biochemical analysis from the subarachnoid space around the spinal cord and ventricular space of the brain. This study compared 15 paired CSF samples in which the CSF from the subarachnoid space via lumbar puncture had higher sodium and chloride levels and lower magnesium and potassium levels than CSF from the ventricles. The differences correlated significantly with the deceased's age and had a similar trend with postmortem interval. This study suggests that CSF from different collection sites has different electrolyte concentrations, which are age and possibly postmortem interval dependent. When collecting CSF, the pathologist should document the collection site, age, and postmortem interval, and the mixing of CSF samples from different sites should be avoided. Further studies are warranted to clarify other possible reasons to explain the observed differences.

Does magnesium sulfate have a role in the management of severe traumatic brain injury in civilian and military populations? A systematic review and meta-analysis.

INTRODUCTION: Traumatic brain injury (TBI) is a significant cause of combat morbidity. Currently, the medical management of TBI is limited to supportive critical care. Magnesium sulfate has been studied as a potentially beneficial therapeutic agent. METHODS: A systematic review and meta-analysis was undertaken, examining the role of magnesium in the management of severe TBI in adults. The primary outcome of the study was all-cause mortality, with secondary outcomes of Glasgow Outcome Score (GOS) and GCS. EMBASE, MEDLINE, CINAHL, WHO Trial Registry and the Cochrane Library database were systematically searched, with data included until 1 February 2017. Inclusion criteria were: human study; aged >13 years; randomised controlled trial; severe TBI. Exclusion criteria were: data collected prior to 1 January 2002; magnesium commenced >24 hours postinjury; magnesium therapy for <24 hours. Statistical analysis was conducted using Stata (V.13.1). RESULTS: The pooled results of six studies found all-cause mortality not to be significantly different in the treatment group (RR 0.84, 95% CI 0.54 to 1.33; P=0.46) with an I2 value of >70%. With regard to the secondary outcomes, no significant difference in GOS scores between treatment and control was demonstrated. GCS showed a significant improvement in the treatment group. CONCLUSIONS: The meta-analysis found a lack of evidence for magnesium pharmacotherapy in severe TBI, although the data were noted to be conflicting and significantly heterogeneous. Further study is recommended to ascertain whether a therapeutic window exists for magnesium in severe TBI.

Metallomic Biomarkers in Cerebrospinal fluid and Serum in patients with Parkinson's disease in Indian population.

Parkinson's disease (PD) is a neurodegenerative disease with the absence of markers for diagnosis. Several studies on PD reported the elements imbalance in biofluids as biomarkers. However, their results remained inconclusive. This study integrates metallomics, multivariate and artificial neural network (ANN) to understand element variations in CSF and serum of PD patients from the largest cohort of Indian population to solve the inconsistent results of previous studies. Also, this study is aimed to (1) ascertain a common element signature between CSF and serum. (2) Assess cross sectional element variation with clinical symptoms. (3) Develop ANN models for rapid diagnosis. A metallomic profile of 110 CSF and 530 serum samples showed significant variations in 10 elements of CSF and six in serum of patients compared to controls. Consistent variations in elements pattern were noticed for Calcium, Magnesium and Iron in both the fluids of PD, which provides feasible diagnosis from serum. Furthermore, implementing multivariate analyses showed clear classification between normal and PD in both the fluids. Also, ANN provides 99% accuracy in detection of disease from CSF and serum. Overall, our analyses demonstrate that elements profile in biofluids of PD will be useful in development of diagnostic markers for PD.

Magnesium Status in Alzheimer's Disease: A Systematic Review.

The interest in poor magnesium (Mg) status as risk factor for Alzheimer's disease (AD) is increasing due to its antioxidant and neuroprotective properties. A systematic PubMed literature search of studies investigating Mg status was undertaken comparing AD to healthy controls (HCs) or patients with medical illness (medical controls [MCs]). Standardized mean differences (SMDs) ± 95% confidence intervals (CIs) were calculated for all outcomes. Of 192 potentially eligible studies, 13 were included (559 patients with AD, 381 HCs, and 126 MCs). Compared to HCs, patients with AD had significantly lower Mg in cerebrospinal fluid (2 studies; SMD = -0.35;P= .02) and in hair (2 studies; SMD = -0.75;P= .0001). No differences between AD and controls were evident for serum Mg. In conclusion, AD seems to be associated with a lower Mg status when compared to HCs, while the scarcity of studies limited the findings about MCs.

Evaluation of Magnesium Levels in Serum and Cerebrospinal Fluid of Patients with Febrile Convulsion Hospitalized in Bahrami Hospital in Tehran in 2010-2011.

Evaluation of magnesium levels in serum and cerebrospinal fluid of patients with febrile convulsion (FC) hospitalized in Bahrami hospital in Tehran in 2010-2011. In the past, decreased levels of magnesium in serum and CSF of patients with FC were reported. The purpose of this study was to identify the possible role of magnesium in febrile seizures in children. Identifying this condition, we may control seizures and also prevent subsequent convulsion. In this cross-sectional study, inclusion criteria were the existence of convulsion due to fever and exclusion criteria were having a known neurological disease which could induce a seizure, and children younger than one month. In each group (cases include children with febrile convulsion and controls include febrile children without convulsion), Mg was measured in blood, and cerebrospinal fluid of 90 children and then they were compared. The data were analyzed by SPSS (α=0.05). The mean serum and CSF levels of Mg in case and control groups were equal (P<0.87 and P<0.22 respectively). There was no difference between two groups in terms of sex, but mean age was significantly different (P<0.003). There was not an association between serum and CSF levels of magnesium and the presence of FC. Therefore, it's not suggested to measure the level of magnesium in serum or CSF in children with fever routinely.

Hypomagnesemia secondary to cerebrospinal fluid losses in a patient with congenital hydrocephalus.

We describe a newborn infant with massive congenital hydrocephalus, presenting with hypomagnesemia secondary to magnesium losses through cerebrospinal fluid (CSF) aspirations. Hypomagnesemia due to CSF losses has not been described in pediatric literature.

Analysis of serum and cerebrospinal fluid in clinically normal adult miniature donkeys.

AIM: To establish reference intervals for serum and cerebrospinal fluid (CSF) parameters in clinically healthy adult miniature donkeys. METHODS: Experiments were conducted on 10 female and 10 male clinically normal adult miniature donkeys, randomly selected from five herds. Lumbosacral CSF collection was performed with the sedated donkey in the standing position. Cell analysis was performed immediately after the samples were collected. Blood samples were obtained from the jugular vein immediately after CSF sample collection. Sodium, potassium, glucose, urea nitrogen, total protein, calcium, chloride, phosphorous and magnesium concentrations were measured in CSF and serum samples. A paired t-test was used to compare mean values between female and male donkeys. RESULTS: The CSF was uniformly clear, colourless and free from flocculent material, with a specific gravity of 1.002. The range of total nucleated cell counts was 2-4 cells/µL. The differential white cell count comprised only small lymphocytes. No erythrocytes or polymorphonuclear cells were observed on cytological examination. Reference values were obtained for biochemical analysis of serum and CSF. Gender had no effect on any variables measured in serum or CSF (p>0.05). CONCLUSION AND CLINICAL RELEVANCE: CSF analysis can provide important information in addition to that gained by clinical examination. CSF analysis has not previously been performed in miniature donkeys; this is the first report on the subject. In the present study, reference intervals for total nucleated cell count, total protein, glucose, urea nitrogen, sodium, potassium, chloride, calcium, phosphorous and magnesium concentrations of serum and CSF were determined for male and female miniature donkeys.

Magnesium and depression: a systematic review.

INTRODUCTION: The incidence of depression is increasing worldwide. Much is still unknown about the possible role of magnesium in depression prevention and treatment. Magnesium has an effect on biological and transduction pathways implicated in the pathophysiology of depression. The possible role of magnesium in depression prevention and treatment remains unclear. OBJECTIVES: We systematically reviewed the possible links between magnesium and depression in humans. METHODS: Twenty-one cross-sectional studies, three intervention trials, one prospective study, one case only study, and one case series study were included based on specific selection criteria. RESULTS: A higher intake of dietary magnesium seems to be associated with lower depression symptoms though reverse causality cannot be excluded. The results assessing the association between blood and cerebrospinal fluid magnesium and depression are inconclusive. DISCUSSION: Magnesium seems to be effective in the treatment of depression but data are scarce and incongruous. Disturbance in magnesium metabolism might be related to depression. Oral magnesium supplementation may prevent depression and might be used as an adjunctive therapy. However, more interventional and prospective studies are needed in order to further evaluate the benefits of magnesium intake and supplementation for depression.

[Role of magnesium in nerve tissue].

The role of magnesium on nerve tissue was discussed. Two main topics of "magnesium and neural activity" and "magnesium-therapy and brain neurons" were described together with introducing our research on rat cultured neurons of cortex and hippocampus.

Changes in cerebrospinal fluid magnesium levels in patients undergoing spinal anaesthesia for hip arthroplasty: does intravenous infusion of magnesium sulphate make any difference? A prospective, randomized, controlled study.

BACKGROUND: Most investigators have attributed the reduced postoperative pain or anaesthetic drug requirements in patients receiving i.v. magnesium sulphate (MgSO(4)) infusion during spinal or general anaesthesia to central N-methyl-d-aspartate (NMDA) receptor magnesium (Mg) activity. In this study, we investigated how cerebrospinal fluid (CSF) Mg concentrations change after spinal anaesthesia, and whether peripherally infusing MgSO(4) influences central Mg levels. METHODS: Forty-five patients undergoing continuous spinal anaesthesia for hip arthroplasty were randomly assigned to receive either i.v. MgSO(4) at a dose of 50 mg kg(-1) diluted in 100 ml 0.9% saline solution followed by 15 mg kg(-1) h(-1) for 6 h or saline at the same volume [mean (sd) 64 (10) ml]. The changes in CSF and serum total and ionized Mg concentrations were assessed at six time points before and after spinal anaesthesia. Secondary outcome variables included serum and CSF electrolytes and proteins. RESULTS: Thirty-five patients completed the study. We found that spinal anaesthesia reduced total and ionized Mg concentrations in CSF by about 10%. Increasing serum Mg concentration over 80% of the baseline value left CSF Mg levels unchanged. CONCLUSIONS: Spinal anaesthesia unexpectedly reduced CSF total and ionized Mg concentrations in patients undergoing hip arthroplasty, although the mechanism is unclear. The dose used for peripheral MgSO(4) infusion in this study had no influence on central Mg concentrations in neurologically healthy patients undergoing spinal anaesthesia. If CSF Mg concentration is a reliable marker of Mg brain bioavailability, peripherally infused MgSO(4) during spinal anaesthesia is unlikely to influence central NMDA receptor activity.

Effect of intrathecal magnesium sulfate solution injection via a microcatheter in the cisterna magna on cerebral vasospasm in the canine subarachnoid haemorrhage model.

OBJECTIVE: To evaluate intracisternal injection of magnesium sulfate (MgSO(4)) solution via a lumbar catheter for the treatment of cerebral vasospasm in the canine subarachnoid haemorrhage (SAH) model. MATERIALS AND METHODS: SAH was induced in 7 beagle dogs using the dual haemorrhage model. Vertebral angiography was repeated on Day 1 (before SAH), and on Day 7 (during cerebral vasospasm) before and 1.5 hours after injection of 0.5 mL/kg of 15 mmol/L MgSO(4) in Ringer solution via the tip of a microcatheter placed in the cisterna magna from the lumbar spine. RESULTS: After injection of MgSO(4) solution, the cerebrospinal fluid magnesium ion concentration significantly increased to 3.89 ± 0.97 mEq/L (P < 0.01) from the baseline value (1.49 ± 0.07 mEq/L). The arterial diameters of the basilar artery (BA), vertebral artery (VA), and superior cerebral artery (SCA) on Day 1 were 1.26 ± 0.19 mm, 1.10 ± 0.13 mm, and 0.74 ± 0.21 mm, respectively. On Day 7 before injection, the arterial diameters of the BA, VA, and SCA significantly decreased to 0.75 ± 0.27 mm, 0.74 ± 0.25 mm, and 0.36 ± 0.21 mm, respectively (P < 0.01), due to vasospasm, and were significantly increased to 0.91 ± 0.27 mm (P < 0.01), 0.91 ± 0.31 mm (P < 0.05), and 0.54 ± 0.14 mm (P < 0.01), respectively, after intracisternal injection of MgSO(4) solution. CONCLUSIONS: Intracisternal MgSO(4) therapy using a microcatheter from the lumbar spine may be effective against vasospasm in the clinical setting of endovascular treatment of ruptured aneurysm.

Investigating paradoxical hysteresis effects in the mouse neocortical slice model.

Clinically, anesthetic drugs show hysteresis in the plasma drug concentrations at induction versus emergence from anesthesia induced unconsciousness. This is assumed to be the result of pharmacokinetic lag between the plasma and brain effect-site and vice versa. However, recent mathematical and experimental studies demonstrate that anesthetic hysteresis might be due in part to lag in the brain physiology, independent of drug transport delay - so-called "neural inertia". The aim of this study was to investigate neural inertia in the reduced neocortical mouse slice model. Seizure-like event (SLE) activity was generated by exposing cortical slices to no-magnesium artificial cerebrospinal fluid (aCSF). Concentration-effect loops were generated by manipulating SLE frequency, using the general anesthetic drug etomidate and by altering the aCSF magnesium concentration. The etomidate (24 µM) concentration-effect relationship showed a clear hysteresis, consistent with the slow diffusion of etomidate into slice tissue. Manipulation of tissue excitability, using either carbachol (50 µM) or elevated potassium (5mM vs 2.5mM) did not significantly alter the size of etomidate hysteresis loops. Hysteresis in the magnesium concentration-effect relationship was evident, but only when the starting condition was magnesium-containing "normal" aCSF. The in vitro cortical slice manifests pathway-dependent "neural inertia" and may be a valuable model for future investigations into the mechanisms of neural inertia in the cerebral cortex.

[Relationship between magnesium concentration in cerebrospinal fluid and delayed cerebral ischemia in patients with aneurysmal subarachnoid hemorrhage].

BACKGROUND: The present study was conducted to determine the relationship between magnesium concentration in cerebrospinal fluid (CSF) and delayed cerebral ischemia (DCI) in patients with subarachnoid hemorrhage (SAH). METHODS: We studied 39 consecutive patients undergoing surgery after SAH. A spinal drainage catheter was inserted into the lower lumbar vertebrae before surgery. CSF was then sampled and the magnesium concentration measured. General clinical data, Hunt-Hess (H-H) grade and Fisher grade, aneurysm size and site, intracerebral and intraventricular hemorrhage, and blood glucose levels were all recorded on admission. At the same time, the Glasgow coma scale (GCS) score was calculated. Outcomes were assessed using the Glasgow outcome scale at discharge. DCI was defined as a two-point decrease in the GCS score and/or focal deficit, and was confirmed by cerebral angiography. The recorded values were expressed as the median (interquartile range). RESULTS: Of the 39 patients, 23 (59%) had DCI. The magnesium concentration in the DCI cases was 2.8 (2.7 and 2.9) mg x dl(-1), which was significantly lower than that in the non-DCI cases, i. e., 2.9 (2.8 and 3.0) mg x dl(-1) (P < 0.05). There were no significant differences in the other factors. CONCLUSIONS: The results indicate that preoperative hypomagnesemia within the CSF might play a role in the development of DCI in patients with SAH; however, further studies will be necessary to confirm this observation.

Is magnesium sulfate by the intrathecal route efficient and safe?

The polypharmacological approach to the treatment of postoperative pain has become routine in an attempt to minimize the adverse side effects of opioids. Magnesium sulphate is a noncompetitive antagonist of the N-methyl-d-aspartate (NMDA) receptor and thus can modify nociceptive modulation. Intravenous administration of magnesium sulphate can improve postoperative analgesia and decrease the requirement for postoperative opiates, but the effects are inconsistent and have not been reliably accompanied by a reduction in the incidence of morphine-related adverse events. Several studies have shown that the administration of magnesium by the intrathecal route is safe and, in combination with opiates, extends the effect of spinal anaesthesia in both animal and human studies. The analysis of these studies justifies further investigation of the use of magnesium sulphate by the intrathecal route.

Temporal profile of the effects of intracisternal injection of magnesium sulfate solution on vasodilation of spastic cerebral arteries in the canine SAH model.

PURPOSE: the temporal profiles of the effects of intracisternal injection of magnesium sulfate (MgSO(4)) on vasodilation and cerebrospinal fluid (CSF) magnesium ion (Mg(2+)) concentration were investigated in the canine subarachnoid hemorrhage (SAH) model. METHOD: cerebral vasospasm was induced using the two-hemorrhage model in seven female beagles. On day 7, 0.5 ml/kg of 15 mmol/l MgSO(4) in Ringer solution was injected into the cerebellomedullary cistern. Angiography was performed on day 1 (before SAH), and before and 1, 3, and 6 h after the intracisternal injection on day 7. CSF Mg(2+) was measured at the same time. RESULTS: the diameters of the basilar artery (BA), vertebral artery (VA), and superior cerebellar artery (SCA) before the intracisternal injection on day 7 were 0.59 ± 0.15, 0.41 ± 0.17, and 0.35 ± 0.17 mm, respectively, and were significantly decreased (p < 0.01) compared with the baseline diameters on day 1. The BA diameters at 1 h (0.74 ± 0.16 mm) and 3 h (0.73 ± 0.13 mm), the VA diameter at 1 h (0.64 ± 0.14 mm), and the SCA diameter at 3 h (0.54 ± 0.08 mm) after the injection were significantly increased (p < 0.05). The CSF Mg(2+) concentration was significantly increased (p < 0.01) at 1 h (3.59 ± 0.76 mEq/l) and 3 h (2.00 ± 0.31 mEq/l) after the injection compared with the baseline value (1.35 ± 0.23 mEq/l). CONCLUSIONS: the reversible effect of intracisternal MgSO(4) solution injection on the spastic artery depends on maintenance of the optimal CSF Mg(2+) concentration.

Concentration of calcium and magnesium and trace elements (zinc, copper, iron and manganese) in cerebrospinal fluid: a try of a pathophysiological classification.

The aim of this study is to analyze the variation of the elements (Ca, Mg, Cu, Fe, Zn and Mn) in normal and pathological CSF and develop a classification basing on the increases in cells and proteins and taking into account these variations. A total of 173 cerebrospinal fluids were analyzed. Of these, 37 fulfilled the criteria of normality and, after clinical exploration, were considered to be healthy (control group). The remaining 136 CSFs (pathological group) belonged to people for whom some neurological pathology had been observed in the clinical exploration and whose CSF analysis presented some abnormality. CSF was extracted by puncture in the lumbar cistern. The analysis of metals was performed by atomic absorption spectrophotometry. The statistical values (mean±standard deviation) obtained for each element analyzed in control group were as follows: Ca (mg/dL): 4.95±0.70; Mg (mg/dL): 2.74±0.10; Cu (µg/dL): 15.70±13.50; Fe (µg/dL): 13.10±3.60; Zn (µg/dL): 17.40±9.50 and Mn (µg/dL): 2.50±0.70. In the pathological CSFs, significant increases were found (p<0.050) in relation to the control group for Ca, Cu, Fe, Zn and Mn in groups with an increase of both cells and proteins. A significant decrease of Mg (p<0.050) was found in the groups with cell and protein increases. Given the results obtained in the different subgroups of the proposed classification, we conclude that it is necessary to further categorize the patients' diagnostics in the different subgroups. This would help to validate the classification.