Association between Serum Malondialdehyde Levels and Mortality in Patients with Severe Brain Trauma Injury

Lorente, Leonardo; Martı́n, Marı́a; Abreu-González, Pedro; Ramos, Luís; Argueso, Mónica; Cáceres, Juan J.; Solé‐Violán, Jordi; Lorenzo, José M.; Molina, Irene García de la Filia; Jiménez, Alejandro

doi:10.1089/neu.2014.3456

Cited by 59 publications

(56 citation statements)

References 23 publications

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“…AIH and rAIH elicit motor plasticity in non-respiratory motor systems following spinal injury (Lovett-Barr et al, 2012; Trumbower et al, 2012; Hayes et al, 2014; Prosser-Loose et al, 2015), and we demonstrated previously increased growth/trophic factor expression associated with dAIH-induced motor plasticity in both respiratory (C 4 ) and non-respiratory (C 7 ) motor nuclei (Lovett-Barr et al, 2012). We now demonstrate similar changes in key growth/trophic factors at other CNS sites associated with non-respiratory motor behaviors, including the motor cortex and non-respiratory (C 7 and L 3 ) spinal motor neurons.…”

Section: Discussionmentioning

confidence: 54%

“…For example, a single presentation of AIH elicits transient increases in sympathetic nerve activity (Dick et al, 2007; Xing and Pilowsky, 2010) and daily AIH (dAIH) for one week elicits prolonged improvement in forelimb function of rats with cervical spinal injuries, an effect that lasts weeks following treatment (Lovett-Barr et al, 2012; Prosser-Loose et al, 2015). A single AIH exposure (15, 1-min hypoxic episodes, 9% inspired O 2 ; 1-min intervals) improves leg strength in persons with chronic spinal injuries (Trumbower et al, 2012), and dAIH (15, 1.5 min episodes per day, 9% O 2 ; 1.5 min intervals) and dAIH paired with 30-min of overground walking practice improved walking speed and endurance in patients with chronic incomplete spinal cord injuries (Hayes et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

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Repetitive acute intermittent hypoxia increases growth/neurotrophic factor expression in non-respiratory motor neurons

et al. 2016

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Repetitive acute intermittent hypoxia (rAIH) increases growth/trophic factor expression in respiratory motor neurons, thereby eliciting spinal respiratory motor plasticity and/or neuroprotection. Here we demonstrate that rAIH effects are not unique to respiratory motor neurons, but are also expressed in non-respiratory, spinal alpha motor neurons and upper motor neurons of the motor cortex. In specific, we used immunohistochemistry and immunofluorescence to assess growth/trophic factor protein expression in spinal sections from rats exposed to AIH three times per week for 10 weeks (3 × wAIH). 3 × wAIH increased brain-derived neurotrophic factor (BDNF), its high-affinity receptor, tropomyosin receptor kinase B (TrkB), and phosphorylated TrkB (pTrkB) immunoreactivity in putative alpha motor neurons of spinal cervical 7 (C7) and lumbar 3 (L3) segments, as well as in upper motor neurons of the primary motor cortex (M1). 3 × wAIH also increased immunoreactivity of vascular endothelial growth factor A (VEGFA), the high-affinity VEGFA receptor (VEGFR-2) and an important VEGF gene regulator, hypoxia-inducible factor-1α (HIF-1α). Thus, rAIH effects on growth/trophic factors are characteristic of non-respiratory as well as respiratory motor neurons. rAIH may be a useful tool in the treatment of disorders causing paralysis, such as spinal injury and motor neuron disease, as a pretreatment to enhance motor neuron survival during disease, or as preconditioning for cell-transplant therapies.

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Section: Discussionmentioning

confidence: 54%

Section: Introductionmentioning

confidence: 99%

Repetitive acute intermittent hypoxia increases growth/neurotrophic factor expression in non-respiratory motor neurons

et al. 2016

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“…They actively regulate macrophages, 17,18 neutrophils, 19,20 dendritic cells, 21-23 and natural killer cells, 24,25 thereby modulating the first line of defense. MSCs also regulate the adaptive immune system, i.e., B and T lymphocytes.…”

Section: Immunosuppressive Properties Of Mesenchymal Stem Cellsmentioning

confidence: 99%

Extrinsic and Intrinsic Mechanisms by Which Mesenchymal Stem Cells Suppress the Immune System

et al. 2016

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Mesenchymal stem cells (MSCs) are a group of fibroblast-like multipotent mesenchymal stromal cells that have the ability to differentiate into osteoblasts, adipocytes, and chondrocytes. Recent studies have demonstrated that MSCs possess a unique ability to exert suppressive and regulatory effects on both adaptive and innate immunity in an autologous and allogeneic manner. A vital step in stem cell transplantation is overcoming the potential graft-versus-host disease, which is a limiting factor to transplantation success. Given that MSCs attain powerful differentiation capabilities and also present immunosuppressive properties, which enable them to survive host immune rejection, MSCs are of great interest. Due to their ability to differentiate into different cell types and to suppress and modulate the immune system, MSCs are being developed for treating a plethora of diseases, including immune disorders. Moreover, in recent years, MSCs have been genetically engineered to treat and sometimes even cure some diseases, and the use of MSCs for cell therapy presents new perspectives for overcoming tissue rejection. In this review, we discuss the potential extrinsic and intrinsic mechanisms that underlie MSCs’ unique ability to modulate inflammation, and both innate and adaptive immunity.

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“…In the multiple logistic regression analysis was found an association between serum MDA levels >2.27 nmol/mL and 30-day mortality (Odds Ratio = 7.23; 95% CI =1.84-28.73; p = 0.005) controlling for GCS and age. We found in the survival analysis that patients with serum MDA higher than 2.27 nmol/mL presented higher mortality at 30 days than patients with lower levels (Hazard ratio = 2.9; 95% CI = 1.31-6.33; p = 0.005).Also in other clinical circumstances, such as patients with sepsis [85,86] and brain trauma injury [87] has been found an association between circulating MDA levels and patient mortality.I think that those higher circulating levels of MDA in patients with MMCAI than in controls and in non-survivors patients than in surviving, represents a higher lipid peroxidation in non-survivors patients.In several clinical trials, ischemic stroke patients were randomized to the administration of different antioxidant vitamins (B2, B6, B12, C, E) or not [88][89][90] …”

mentioning

confidence: 59%

“…Also in other clinical circumstances, such as patients with sepsis [85,86] and brain trauma injury [87] has been found an association between circulating MDA levels and patient mortality.…”

Section: Malondialdehydementioning

confidence: 96%

New prognostic biomarkers in patients with ischemic stroke

Lorente

2016

Mol Med Chem

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Ischemic stroke leads to disability and mortality and involved great consumption of resources. This review focuses on new prognostic biomarkers of mortality in patients with ischemic stroke in relation to the inflammation, coagulation, and oxidation. Blood concentration of tissue inhibitor of matrix metalloproteinases (TIMP)-1, soluble CD154 (sCD154), and malondialdehyde (MDA) in ischemic stroke patients have been recently found to be associated with mortality. Matrix metalloproteinases (MMPs) are zinc-containing endoproteinases involved in neuroinflammation during cerebral ischemia and TIMP-1 is the inhibitor of some of them. sCD154 is a member of the tumor necrosis factor (TNF) family that is released into circulation from different cells and when binding to their cell surface receptor showed proinflamatory and procoagulant properties. MDA is a low molecular weight aldehyde and appears due to the attacks from free radical to phospholipids of cellular membrane. The determination of circulating levels of those biomarkers could help in the prognostic classification of the patients. In addition, the modulation of those pathways could open new research lines for the treatment of ischemic stroke patients.Keywords: Ischemic stroke; biomarkers; TIMP-1; sCD154; malondialdehyde To cite this article: Leonardo Lorente. New prognostic biomarkers in patients with ischemic stroke. Mol Med Chem 2015; 1: e972. doi: 10.14800/mmc.972. IntroductionIschemic stroke leads to disability and mortality and involved great consumption of resources [1] . This review focuses on new prognostic biomarkers of mortality in patients with ischemic stroke in relation to the inflammation, coagulation, and oxidation. Tissue inhibitor of matrix metalloproteinases-1Matrix metalloproteinases (MMPs) are zinc-containing endoproteinases, which could be classified according to the substrate specificity in gelatinases (MMP-2 and MMP-9), collagenases (MMP-1, MMP-8 and MMP-13), stromelysins (MMP-3, MMP-10, MMP-11), matrilysins (MMP-7), elastases (MMP-12) and membrane-type (MMP-14, MMP-15, MMP-16 and MMP-17). MMPs are involved in the processes of degradation and remodelling of the extracellular matrix (ECM). MMP activity is regulated by tissue inhibitor of matrix metalloproteinases (TIMPs). MMPs are involved in physiological functions such as morphogenesis, tissue remodelling, menstrual cycle, and angiogenesis; and also in different diseases as tumour, arthritis, sepsis, and atherosclerosis [2] .Cerebral ischemia activate an inflammatory response and are released different cytotoxic agents, such as MMPs, which could favorate disruption of the blood-brain barrier (BBB) and cell damage [3] .There have been found higher circulating MMP-9 levels in ischemic stroke patients than in controls [4][5][6][7][8] , and also in patients with ischemic stroke and worse functional outcome compared with patients with better outcome [4][5][6][7][8][9][10][11][12] . Also, higher circulating levels of MMP-10 in ischemic stroke patients than in controls there have been f...

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Association between Serum Malondialdehyde Levels and Mortality in Patients with Severe Brain Trauma Injury

Cited by 59 publications

References 23 publications

Repetitive acute intermittent hypoxia increases growth/neurotrophic factor expression in non-respiratory motor neurons

Repetitive acute intermittent hypoxia increases growth/neurotrophic factor expression in non-respiratory motor neurons

Extrinsic and Intrinsic Mechanisms by Which Mesenchymal Stem Cells Suppress the Immune System

New prognostic biomarkers in patients with ischemic stroke

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