Skip to main navigation menu Skip to main content Skip to site footer

Mini Review

Vol. 2 No. 1 (2024): January/March - 2024

A Mini-Review of Magnesium Sulfate's Anti-Inflammatory, Immune, and Neuroprotective Mechanisms in Subarachnoid Hemorrhage

DOI
https://doi.org/10.52600/2965-0968.bjcmr.2024.2.1.12-17
Submitted
September 9, 2023
Published
2023-10-18

Abstract

Subarachnoid hemorrhage (SAH) is a severe neurological condition frequently associated with devastating complications. This mini-review explores the therapeutic potential of magnesium sulfate (MS) in this setting. We conducted an updated search across several academic databases, focusing on articles examining MS's anti-inflammatory, immune-modulating, and neuroprotective properties in this setting. The findings suggested that MS can inhibit specific inflammatory pathways, reduce pro-inflammatory markers, modulate immune responses by inhibiting microglial activation, and offer neuroprotection through mechanisms such as NMDA receptor antagonism. However, despite the promising aspects of MS for SAH complications management, available clinical studies yield inconsistent outcomes. Additional research is necessary for full clinical validation.

References

  1. Chan AY, Choi EH, Yuki I, Suzuki S, Golshani K, Chen JW, et al. Cerebral vasospasm after subarachnoid hemorrhage: De-veloping treatments. Brain Hemorrhages. 2021;2(1):15–23.
  2. Yamada H, Kase Y, Okano Y, Kim D, Goto M, Takahashi S, Okano H, Toda M. Subarachnoid hemorrhage triggers neuroin-flammation of the entire cerebral cortex, leading to neuronal cell death. Inflamm Regen. 2022 Dec 14;42(1):61
  3. Wong GK, Boet R, Poon WS, Chan MT, Gin T, Ng SC, Zee BC. Intravenous magnesium sulphate for aneurysmal subarachnoid hemorrhage: an updated systemic review and meta-analysis. Crit Care. 2011;15(1):R52.
  4. Takeuchi S, Kumagai K, Toyooka T, Otani N, Wada K, Mori K. Intravenous Hydrogen Therapy With Intracisternal Magnesium Sulfate Infusion in Severe Aneurysmal Subarachnoid Hemorrhage. Stroke. 2021 Jan;52(1):20-27.
  5. Altura BM, Gebrewold A, Zhang A, Altura BT. Low extracellular magnesium ions induce lipid peroxidation and activation of nuclear factor-kappa B in canine cerebral vascular smooth muscle: possible relation to traumatic brain injury and strokes. Neurosci Lett. 2003 May 8;341(3):189-92.
  6. Pawlowska E, Szczepanska J, Wisniewski K, Tokarz P, Jaskólski DJ, Blasiak J. NF-κB-Mediated Inflammation in the Patho-genesis of Intracranial Aneurysm and Subarachnoid Hemorrhage. Does Autophagy Play a Role? Int J Mol Sci. 2018 Apr19;19(4):1245.
  7. Romoli M, Giammello F, Mosconi MG, De Mase A, De Marco G, Digiovanni A, et al. Immunological profile of vasospasm after subarachnoid hemorrhage. International Journal of Molecular Sciences. 2023;24(10):8856.
  8. Li Y, Wu P, Bihl JC, Shi H. Underlying Mechanisms and Potential Therapeutic Molecular Targets in Blood-Brain Barrier Disruption after Subarachnoid Hemorrhage. Curr Neuropharmacol. 2020;18(12):1168-1179.
  9. Chang YY, Jean WH, Lu CW, Lin TY. Magnesium sulfate enhances lipopolysaccharide tolerance. Eur J Inflamm. 2023;21:1-5.
  10. Peraçoli JC, Silva PB, Neves HM, Borges VTM, Abbade JF, Costa RAA, et al. Modulatory effect of two regimens of magnesium sulfate on the systemic inflammatory response in pregnant women with imminent eclampsia. Pregnancy Hypertension. 2022;29:46–53.
  11. Lv SY, Wu Q, Liu JP, Shao J, Wen LL, Xue J, Zhang XS, Zhang QR, Zhang X. Levels of Interleukin-1β, Interleukin-18, and Tumor Necrosis Factor-α in Cerebrospinal Fluid of Aneurysmal Subarachnoid Hemorrhage Patients May Be Predictors of Early Brain Injury and Clinical Prognosis. World Neurosurg. 2018 Mar;111:e362-e373.
  12. Zhang R, Zhang Y, Liu Z, Pei Y, He Y, Yu J, et al. Plasma interleukin 6 levels predict long-term mortality in aneurysmal subarachnoid. 2022.
  13. Muroi C, Burkhardt JK, Hugelshofer M, Seule M, Mishima K, Keller E. Magnesium and the inflammatory response: potential pathophysiological implications in the management of patients with aneurysmal subarachnoid hemorrhage? Magnes Res. 2012 Jul;25(2):64-71.
  14. Wang LC, Huang CY, Wang HK, Wu MH, Tsai KJ. Magnesium sulfate and nimesulide have synergistic effects on rescuing brain damage after transient focal ischemia. J Neurotrauma. 2012 May 1;29(7):1518-29.
  15. Sun X, Mei Y, Tong E. Effect of magnesium on nitric oxide synthase of neurons in cortex during early period of cerebral ischemia. J Tongji Med Univ. 2000;20(1):13-5, 42.
  16. Maier JAM, Locatelli L, Fedele G, Cazzaniga A, Mazur A. Magnesium and the Brain: A Focus on Neuroinflammation and Neurodegeneration. Int J Mol Sci. 2023 Dec 23;24(1):223.
  17. Ayer R, Jadhav V, Sugawara T, Zhang JH. The neuroprotective effects of cyclooxygenase-2 inhibition in a mouse model of aneurysmal subarachnoid hemorrhage. Intracerebral Hemorrhage Research. 2011;145–9.
  18. Iqbal S, Hayman EG, Hong C, Stokum JA, Kurland DB, Gerzanich V, Simard JM. Inducible nitric oxide synthase (NOS-2) in subarachnoid hemorrhage: Regulatory mechanisms and therapeutic implications. Brain Circ. 2016;2(1):8-19.
  19. Huang CY, Hsieh YL, Ju DT, Lin CC, Kuo CH, Liou YF, Ho TJ, Tsai CH, Tsai FJ, Lin JY. Attenuation of Magnesium Sulfate on CoCl₂-Induced Cell Death by Activating ERK1/2/MAPK and Inhibiting HIF-1α via Mitochondrial Apoptotic Signaling Su-ppression in a Neuronal Cell Line. Chin J Physiol. 2015 Aug 31;58(4):244-53.
  20. Solár P, Zamani A, Lakatosová K, et al. The blood–brain barrier and the neurovascular unit in subarachnoid hemorrhage: molecular events and potential treatments. Fluids Barriers CNS. 2022;19:29.
  21. Gao F, Ding B, Zhou L, Gao X, Guo H, Xu H. Magnesium sulfate provides neuroprotection in lipopolysaccharide-activated primary microglia by inhibiting NF-κB pathway. J Surg Res. 2013 Oct;184(2):944-50.
  22. Naser SA, Abdelsalam A, Thanigachalam S, Naser AS, Alcedo K. Domino effect of hypomagnesemia on the innate immunity of Crohn’s disease patients. World J Diabetes. 2014;5(4):527-535.
  23. Small C, Scott K, Smart D, Sun M, Christie C, Lucke-Wold B. Microglia and Post-Subarachnoid Hemorrhage Vasospasm: Review of Emerging Mechanisms and Treatment Modalities. Clin Surg J. 2022;3(3):INF1000213.
  24. Unda SR, Birnbaum J, Labagnara K, Wong M, Vaishnav DP, Altschul DJ. Peripheral Monocytosis at Admission to Predict Cerebral Infarct and Poor Functional Outcomes in Subarachnoid Hemorrhage Patients. World Neurosurg. 2020;138:e523-e529.
  25. Xu R, Wang L, Sun L, Dong J. Neuroprotective effect of magnesium supplementation on cerebral ischemic diseases. Life Sciences. 2021;272:119257.
  26. Maier JAM. Endothelial cells and magnesium: implications in atherosclerosis. Clin Sci (Lond). 2012;122(9):397-407.
  27. Maier JAM, Malpuech-Brugère C, Zimowska W, Rayssiguier Y, Mazur A. Low magnesium promotes endothelial cell dys-function: implications for atherosclerosis, inflammation and thrombosis. Biochim Biophys Acta (BBA) - Mol Basis Dis. 2004;1689(1):13-21.
  28. Maier JA, Castiglioni S, Locatelli L, Zocchi M, Mazur A. Magnesium and inflammation: Advances and perspectives. Semin Cell Dev Biol. 2021 Jul;115:37-44
  29. Davalos Bichara M, Goldman RD. Magnesium for treatment of asthma in children. Can Fam Physician. 2009 Sep;55(9):887-889.
  30. Li X, Liu H, Yang Y. Magnesium sulfate attenuates brain edema by lowering AQP4 expression and inhibits glia-mediated neuroinflammation in a rodent model of Eclampsia. Behavioural Brain Research. 2019;364:403–12.
  31. Li X, Han X, Yang J, Bao J, Di X, Zhang G, Liu H. Magnesium Sulfate Provides Neuroprotection in Eclampsia-Like Seizure Model by Ameliorating Neuroinflammation and Brain Edema. Mol Neurobiol. 2017 Dec;54(10):7938-7948.
  32. Jin J, Duan J, Du L, Xing W, Peng X, Zhao Q. Inflammation and immune cell abnormalities in intracranial aneurysm sub-arachnoid hemorrhage (SAH): Relevant signaling pathways and therapeutic strategies. Frontiers in Immunology. 2022;13.
  33. Lingam I, Robertson NJ. Magnesium as a neuroprotective agent: A review of its use in the fetus, term infant with neonatal encephalopathy, and the adult stroke patient. Dev Neurosci. 2018;40(1):1-12
  34. Mallah K, Couch C, Borucki DM, Toutonji A, Alshareef M, Tomlinson S. Anti-inflammatory and Neuroprotective Agents in Clinical Trials for CNS Disease and Injury: Where Do We Go From Here? Front Immunol. 2020 Sep 10;11:2021.
  35. Kawakita F, Kanamaru H, Asada R, Suzuki Y, Nampei M, Nakajima H, Oinaka H, Suzuki H. Roles of glutamate in brain injuries after subarachnoid hemorrhage. Histol Histopathol. 2022 Nov;37(11):1041-1051.
  36. Koning G, Lyngfelt E, Svedin P, Leverin A, Jinnai M, Gressens P, et al. Magnesium sulphate induces preconditioning in preterm rodent models of cerebral hypoxia‐ischemia. International Journal of Developmental Neuroscience. 2018;70(1):56–66.
  37. Westermaier T, Stetter C, Vince GH, Pham M, Tejon JP, Eriskat J, Kunze E, Matthies C, Ernestus RI, Solymosi L, Roosen K. Prophylactic intravenous magnesium sulfate for treatment of aneurysmal subarachnoid hemorrhage: a randomized, place-bo-controlled, clinical study. Crit Care Med. 2010 May;38(5):1284-90.
  38. Lucke-Wold B, Poe J, Sriram S, Mehkri Y. Electrolyte imbalance and neurologic injury. CNS & Neurological Disorders - Drug Targets. 2023;22.
  39. Elsayed NA, Boyer TM, Burd I. Fetal Neuroprotective Strategies: Therapeutic Agents and Their Underlying Synaptic Pathways. Front Synaptic Neurosci. 2021 Jun 23;13:680899.
  40. Yamanaka R, Shindo Y, Oka K. Magnesium Is a Key Player in Neuronal Maturation and Neuropathology. International Journal of Molecular Sciences. 2019; 20(14):3439.
  41. Wu F, Liu Z, Li G, Zhou L, Huang K, Wu Z, Zhan R, Shen J. Inflammation and Oxidative Stress: Potential Targets for Improving Prognosis After Subarachnoid Hemorrhage. Front Cell Neurosci. 2021 Sep 24;15:739506.
  42. Schmitt HJ, Barth GR, Thierauf P. Neuronal Protection by Intraischemic Brain Perfusion: An Electron Microscopy Study in the Rat. J Neurosurg Anesthesiol. 1994;6(4):265-274.
  43. Stanojević M, Lopicic S, Spasic S, Aleksic I, Nedeljkov V, Prostran M. Effects of high extracellular magnesium on electro-physiological properties of membranes of Retzius neurons in leech Haemopis sanguisuga. J Elem. 2016;1(20):887.
  44. Dodd WS, Laurent D, Dumont AS, Hasan DM, Jabbour PM, Starke RM, et al. Pathophysiology of delayed cerebral ischemia after subarachnoid hemorrhage: A Review. Journal of the American Heart Association. 2021;10(15).
  45. Euser AG, Cipolla MJ. Magnesium sulfate for the treatment of eclampsia: a brief review. Stroke. 2009 Apr;40(4):1169-75.
  46. Rovsing AH, Savran O, Ulrik CS. Magnesium sulfate treatment for acute severe asthma in adults-a systematic review and meta-analysis. Front Allergy. 2023 Jul 28;4:1211949.
  47. Dorhout Mees SM, Algra A, Vandertop WP, van Kooten F, Kuijsten HA, Boiten J, van Oostenbrugge RJ, Al-Shahi Salman R, Lavados PM, Rinkel GJ, van den Bergh WM; MASH-2 Study Group. Magnesium for aneurysmal subarachnoid haemorrhage (MASH-2): a randomised placebo-controlled trial. Lancet. 2012 Jul 7;380(9836):44-9.
  48. Yamamoto T, Mori K, Esaki T, Nakao Y, Tokugawa J, Watanabe M. Preventive effect of continuous cisternal irrigation with magnesium sulfate solution on angiographic cerebral vasospasms associated with aneurysmal subarachnoid hemorrhages: a randomized controlled trial. J Neurosurg. 2016;124(1):18-26.
  49. Soliman R, Zohry G. Effect of magnesium sulphate and milrinone on cerebral vasospasm after aneurysmal subarachnoid hemorrhage: a randomized study. Braz J Anesthesiol. 2019 Jan-Feb;69(1):64-71.