Effect of magnesium, MK-801 and combination of magnesium and MK-801 on blood–brain barrier permeability and brain edema after experimental traumatic diffuse brain injury

İmer, Murat; Omay, Bulent; Uzunkol, Ajlan; Erdem, Tamer; Sabancı, Pulat Akın; Karasu, Aykut; Albayrak, Serdar Baki; Sencer, Altay; Hepgül, Kemal; Kaya, Mehmet

doi:10.1179/174313209x385617

Cited by 45 publications

(24 citation statements)

References 24 publications

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“…29 A previous study demonstrated that early intervention with Cerebrolysin reduces the BBB permeability and diminishes brain edema and other brain pathology, which contributes to recovery of sensorimotor function after TBI induced by a stab cerebral injury. 56 In the present study, Cerebrolysin treatment significantly increased the percentage of FITC-dextran-perfused vessels in the brain cortex, indicating that Cerebrolysin enhances the microvascular patency of the brain after CHI.…”

Section: Discussionmentioning

confidence: 99%

Improvement in functional recovery with administration of Cerebrolysin after experimental closed head injury

Zhang¹,

Chopp

Meng³

et al. 2013

JNS

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Object Cerebrolysin is a unique peptide preparation that mimics the action of neurotrophic factors. This study was designed to investigate the effects of acute treatment of experimental closed head injury (CHI) in rats with Cerebrolysin on neurological function. Methods Adult male Wistar rats (n = 60) were subjected to impact acceleration–induced CHI. Closed head injured rats received intraperitoneal injection of saline (n = 30) or Cerebrolysin (2.5 ml/kg, n = 30) starting 1 hour postinjury and administered once daily until they were killed (2 or 14 days after CHI). To evaluate functional outcome, the modified neurological severity score (mNSS), foot fault, adhesive removal, and Morris water maze (MWM) tests were performed. Animals were killed on Day 14 (n = 20) after injury, and their brains were removed and processed for measurement of neuronal cells, axonal damage, apoptosis, and neuroblasts. The remaining rats (n = 40) were killed 2 days postinjury to evaluate cerebral microvascular patency by fluorescein isothiocyanate (FITC)–dextran perfusion (n = 16) and to measure the expression of vascular endothelial growth factor (VEGF) and matrix metalloproteinase–9 (MMP-9) by using real-time reverse transcriptase-polymerase chain reaction (RT-PCR, n = 8) and by immunohistochemical analysis (n = 16). Results At 14 days post-CHI, the Cerebrolysin treatment group exhibited significant improvements in functional outcomes (the adhesive removal, mNSS, foot-fault, and MWM tests), and significantly more neurons and neuroblasts were present in the dentate gyrus (DG) (p < 0.05) compared with the saline-treated group (p < 0.05). At 2 days post-CHI, the Cerebrolysin group exhibited a significantly higher percentage of phosphorylated neurofilament H (pNF-H)–positive staining area in the striatum (p < 0.05), a significant increase in the percentage of FITC-dextran perfused vessels in the brain cortex (p < 0.05), a significant increase in the number of VEGF-positive cells (p < 0.05), and a significant reduction in the MMP-9 staining area (p < 0.05) compared with the saline-treated group. There was no significant difference in mRNA levels of MMP-9 and VEGF in the hippocampus and cortex 48 hours postinjury between Cerebrolysin- and saline-treated rats that sustained CHI. Conclusions Acute Cerebrolysin treatment improves functional recovery in rats after CHI. Cerebrolysin is neuroprotective for CHI (increased neurons in the dentate gyrus and the CA3 regions of the hippocampus and increased neuroblasts in the dentate gyrus) and may preserve axonal integrity in the striatum (significantly increased percentage of pNF-H–positive tissue in the striatum). Reduction of MMP-9 and elevation of VEGF likely contribute to enhancement of vascular patency and integrity as well as neuronal survival induced by Cerebrolysin. These promising results suggest that Cerebrolysin may be a useful treatment in improving the recovery of patients with CHI.

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Section: Discussionmentioning

confidence: 99%

Improvement in functional recovery with administration of Cerebrolysin after experimental closed head injury

Zhang¹,

Chopp

Meng³

et al. 2013

JNS

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“…This could imply that, in addition to influencing hemostasis, Mg might have possible neuroprotective effects for patients with ICH 24. Preclinical data suggest that Mg exhibits multiple complementary neuroprotective mechanisms, including inhibition of glutamate release,25 restoration of blood‐brain barrier integrity, decrease in brain edema,26 and noncompetitive antagonism of N‐methyl‐ d ‐aspartate receptor activation via blockage of voltage‐dependent calcium channels 24, 27. Moreover, the antihypertensive effect of Mg could be protective in patients with ICH 24…”

Section: Discussionmentioning

confidence: 99%

Serum Magnesium Levels and Outcomes in Patients With Acute Spontaneous Intracerebral Hemorrhage

Goyal

Tsivgoulis

Malhotra

et al. 2018

JAHA

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BackgroundMagnesium (Mg) has potential hemostatic properties. We sought to investigate the potential association of serum Mg levels (at baseline and at 48 hours) with outcomes in patients with acute spontaneous intracerebral hemorrhage (ICH).Methods and ResultsWe reviewed data on all patients with spontaneous ICH with available Mg levels at baseline, over a 5‐year period. Clinical and radiological outcome measures included initial hematoma volume, admission National Institutes of Health Stroke Scale and ICH scores, in‐hospital mortality, favorable functional outcome (modified Rankin Scale scores, 0–1), and functional independence (modified Rankin Scale scores, 0–2) at discharge. Our study population consisted of 299 patients with ICH (mean age, 61±13 years; mean admission serum Mg, 1.8±0.3 mg/dL). Increasing admission Mg levels strongly correlated with lower admission National Institutes of Health Stroke Scale score (Spearman's r, −0.141; P=0.015), lower ICH score (Spearman's r, −0.153; P=0.009), and lower initial hematoma volume (Spearman's r, −0.153; P=0.012). Higher admission Mg levels were documented in patients with favorable functional outcome (1.9±0.3 versus 1.8±0.3 mg/dL; P=0.025) and functional independence (1.9±0.3 versus 1.8±0.3 mg/dL; P=0.022) at discharge. No association between serum Mg levels at 48 hours and any of the outcome variables was detected. In multiple linear regression analyses, a 0.1‐mg/dL increase in admission serum Mg was independently and negatively associated with the cubed root of hematoma volume at admission (regression coefficient, −0.020; 95% confidence interval, −0.040 to −0.000; P=0.049) and admission ICH score (regression coefficient, −0.053; 95% confidence interval, −0.102 to −0.005; P=0.032).ConclusionsHigher admission Mg levels were independently related to lower admission hematoma volume and lower admission ICH score in patients with acute spontaneous ICH.

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“…It has been reported that magnesium improves functional outcome following blood brain barrier disruption and decrease brain edema (13). Studies on the effect of magnesium or hypertonic saline in experimental models commonly applied intraperitoneal or intra-arterial way of drug administration (13,14). However, the efficacy of intraventricular hypertonic saline and magnesium on brain cell damage in severe head injury has not been evaluated yet.…”

Section: Introductionmentioning

confidence: 99%

Comparing Effects of Intraventricular Hypertonic Saline and Magnesium Sulfate Application on Diffuse Brain Injury in Rats

Kızılcık¹,

Çelikoğlu²,

Keleştemur³

et al. 2017

tybdd

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Objective: Diffuse brain injury is one of the most common issues encountered in, patients with trauma and it leads to morbidity and mortality via increased intracranial pressure. The aim of the study was to compare the effects of magnesium sulfate and hypertonic saline on diffuse brain injury in rats. Materials and Methods: In this study 18 male Sprague-Dawley rats weighing 250-300 g were used. The rats were randomly divided into trauma (control), trauma+magnesium, and trauma+hypertonic saline groups. Traumatic brain injury was induced by modified Feeney head trauma model. A single dose of 10 µL isotonic saline, magnesium sulphate and hypertonic saline were applied intraventricularly to the control, magnesium, and hypertonic saline groups, respectively. Rats were decapitated 24 hours after the head trauma. Their brains were dissected immediately and stored with dry ice at -80 °C for histopathological experiments. Results: The number of damaged neurons were significantly higher in both control and hypertonic saline groups (p=0.001, p=0.008). However, the number of damaged neurons did not show significant difference between hypertonic saline and control groups, it was significantly lower in magnesium group (p<0.05). Conclusion: In this study, intraventricular magnesium application is found effective in reducing the number of the damaged neurons in rat traumatic brain injury model. These results suggest that magnesium usage may be evaluated for the treatment of patients with traumatic brain injury in further prospective studies.

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Effect of magnesium, MK-801 and combination of magnesium and MK-801 on blood–brain barrier permeability and brain edema after experimental traumatic diffuse brain injury

Abstract: The present data demonstrate that treatment with magnesium, MK-801 and combination of magnesium and MK-801 can reduce formation of brain edema and can help restore BBB permeability after experimental diffuse brain injury.

Cited by 45 publications

References 24 publications

Improvement in functional recovery with administration of Cerebrolysin after experimental closed head injury

Improvement in functional recovery with administration of Cerebrolysin after experimental closed head injury

Serum Magnesium Levels and Outcomes in Patients With Acute Spontaneous Intracerebral Hemorrhage

Comparing Effects of Intraventricular Hypertonic Saline and Magnesium Sulfate Application on Diffuse Brain Injury in Rats

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