The Effect of Human Umbilical Cord Blood Cells on Survival and Cytokine Production by Post-Ischemic Astrocytes in Vitro

Jiang, Lixian; Saporta, Samuel; Chen, Ning; Sanberg, Cyndy D.; Sanberg, Paul R.; Willing, Alison E.

doi:10.1007/s12015-010-9174-x

Cited by 11 publications

(5 citation statements)

References 55 publications

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“…Increased TNF-α has been observed in other experimental models such as those for ionizing radiation [21-25] and ischemia [26]. Inhibition of TNF-α levels by drug treatment or antibody neutralization results in an improvement in bone marrow regeneration after radiation exposure [25].…”

Section: Discussionmentioning

confidence: 99%

17-DMAG diminishes hemorrhage-induced small intestine injury by elevating Bcl-2 protein and inhibiting iNOS pathway, TNF-α increase, and caspase-3 activation

et al. 2011

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BackgroundHemorrhage increases inducible nitric oxide synthase (iNOS) and depletes ATP levels in various tissues. Previous studies have shown that geldanamycin, an inducer of heat shock protein 70kDa (HSP-70) and inhibitor of iNOS, limits both processes. Reduction in NO production limits lipid peroxidation, apoptosome formation, and caspase-3 activation, thereby increasing cellular survival and reducing the sequelae of hemorrhage. The poor solubility of geldanamycin in aqueous solutions, however, limits its effectiveness as a drug. 17-DMAG is a water-soluble analog of geldanamycin that might have greater therapeutic utility. This study investigated the effectiveness of 17-DMAG at reducing hemorrhagic injury in mouse small intestine.ResultsIn mice, the hemorrhage-induced iNOS increase correlated with increases in Kruppel-like factor 6 (KLF6) and NF-kB and a decrease in KLF4. As a result, increases in NO production and lipid peroxidation occurred. Moreover, hemorrhage also resulted in decreased Bcl-2 and increased TNF-α, IL-6, and IL-10 concentrations, p53 protein, caspase-3 activation, and cellular ATP depletion. A shortening and widening of villi in the small intestine was also observed. Treatment with 17-DMAG significantly reduced the hemorrhage-induced increases in iNOS protein, jejunal alteration, and TNF-α and IL-10 concentrations, but 17-DMAG did not affect the hemorrhage-induced increases in p53 and IL-6 concentration. 17-DMAG treatment by itself upregulated HSP-70, Bcl-2, and p53.ConclusionSince 17-DMAG is water soluble, bioactive, and not toxic, 17-DMAG may prove useful as a prophylactic drug for hemorrhage.

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Section: Discussionmentioning

confidence: 99%

17-DMAG diminishes hemorrhage-induced small intestine injury by elevating Bcl-2 protein and inhibiting iNOS pathway, TNF-α increase, and caspase-3 activation

et al. 2011

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“…Among them, modulation of immune responses emerges as a key feature of UCBC therapy for neonatal HI brain injury. UCBCs can reduce survival of microglia after hypoxia in vitro (Jiang et al , 2010), and inhibit activation of microglia in the cerebral cortex after hypoxiaischemia in neonatal rats (Pimentel-Coelho et al , 2010). Administration of human UCBCs modulates the balance of neuroinflammation, attenuates reactive gliosis, and down-regulates the expression of the major astrocytic gap junction protein connexin 43, which in turn restores BBB function and substantially reduces the inflammatory cell influx into the brain (Wasielewski et al , 2012).…”

Section: Bench To Bedside: Promising Anti-inflammatory/immunomodulmentioning

confidence: 99%

Brain-immune interactions in perinatal hypoxic-ischemic brain injury

Concepcion

Meng

et al. 2017

Progress in Neurobiology

187

189

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Perinatal hypoxia-ischemia remains the primary cause of acute neonatal brain injury, leading to a high mortality rate and long-term neurological deficits, such as behavioral, social, attentional, cognitive and functional motor deficits. An ever-increasing body of evidence shows that the immune response to acute cerebral hypoxia-ischemia is a major contributor to the pathophysiology of neonatal brain injury. Hypoxia-ischemia provokes an intravascular inflammatory cascade that is further augmented by the activation of resident immune cells and the cerebral infiltration of peripheral immune cells response to cellular damages in the brain parenchyma. This prolonged and/or inappropriate neuroinflammation leads to secondary brain tissue injury. Yet, the long-term effects of immune activation, especially the adaptive immune response, on the hypoxic-ischemic brain still remain unclear. The focus of this review is to summarize recent advances in the understanding of post-hypoxic-ischemic neuroinflammation triggered by the innate and adaptive immune responses and to discuss how these mechanisms modulate the brain vulnerability to injury. A greater understanding of the reciprocal interactions between the hypoxic-ischemic brain and the immune system will open new avenues for potential immunomodulatory therapy in the treatment of neonatal brain injury.

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“…UCB cells also influence the function of astrocytes. When UCB MNCs were grown in an indirect co-culture system with astrocytes, IL-6 increased significantly in the normoxic cultures, but not in the cultures exposed to OGD (Jiang et al 2011). Under hypoxic/ischemic conditions, the presence of UCB cells induced an increase in IL-10 concentration.…”

Section: Cord Blood Effects On Cns Inflammationmentioning

confidence: 91%