Intra-parenchymal injection of tumor necrosis factor-? and interleukin 1-? produces dopamine neuron loss in the rat

Carvey, Paul M.; Chen, E.-Y.; Lipton, Jack W.; Tong, Chong Wai; Chang, Qing; Ling, Zaodung

doi:10.1007/s00702-004-0222-z

Cited by 73 publications

(54 citation statements)

References 35 publications

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“…Successful outcomes of neural stem cell grafts in restoration of function after 6-OHDA-induced nigrostriatal degeneration has been attributed to a combination of neural differentiation and trophic factor production (Yasuhara, Matsukawa et al 2006) in large part based on the observation that a large fraction of adult neural stem cells within transplanted grafts retain detectable nestin expression and never fully mature post-transplantation. Likewise, the in vivo neuroprotective effects of other cell types with demonstrated in vitro multi-lineage potential, including mesenchymal stem cells (MSC) (Scuteri, Cassetti et al 2006), umbilical cord matrix stem cells (Weiss, Medicetty et al 2006), and bone marrow derived stromal cells (BMSCs) (Garcia, Aguiar et al 2004;Carvey, Chen et al 2005;Ye, Chen et al 2005), has been shown to be mediated in part through a mechanism of trophic support.…”

Section: Discussionmentioning

confidence: 99%

Autologous transplants of Adipose-Derived Adult Stromal (ADAS) cells afford dopaminergic neuroprotection in a model of Parkinson's disease

McCoy

Martinez

Ruhn

et al. 2008

Experimental Neurology

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Adult adipose contains stromal progenitor cells with neurogenic potential. However, the stability of neuronal phenotypes adopted by Adipose-Derived Adult Stromal (ADAS) cells and whether terminal neuronal differentiation is required for their consideration as alternatives in cell replacement strategies to treat neurological disorders is largely unknown. We investigated whether in vitro neural induction of ADAS cells determined their ability to neuroprotect or restore function in a lesioned dopaminergic pathway. In vitro-expanded naïve or differentiated ADAS cells were autologously transplanted into substantia nigra 1-week after an intrastriatal 6-hydroxydopamine injection. Neurochemical and behavioral measures demonstrated neuroprotective effects of both ADAS grafts against 6-hydroxydopamine-induced dopaminergic neuron death, suggesting that pre-transplantation differentiation of the cells does not determine their ability to survive or neuroprotect in vivo. Therefore, we investigated whether equivalent protection by naïve and neurally-induced ADAS grafts resulted from robust in situ differentiation of both graft types into dopaminergic fates. Immunohistological analyses revealed that ADAS cells did not adopt dopaminergic cell fates in situ, consistent with the limited ability of these cells to undergo terminal differentiation into electrically active neurons in vitro. Moreover, re-exposure of neurally-differentiated ADAS cells to serum-containing medium in vitro confirmed ADAS cell phenotypic instability (plasticity). Lastly, given that gene expression analyses of in vitro-expanded ADAS cells revealed that both naïve and differentiated ADAS cells express potent dopaminergic survival factors, ADAS transplants may have exerted neuroprotective effects by production of trophic factors at the lesion site. ADAS cells may be ideal for ex vivo gene transfer therapies in Parkinson's disease treatment.

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Section: Discussionmentioning

confidence: 99%

Autologous transplants of Adipose-Derived Adult Stromal (ADAS) cells afford dopaminergic neuroprotection in a model of Parkinson's disease

McCoy

Martinez

Ruhn

et al. 2008

Experimental Neurology

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“…For instance, intraparenchymal injection of TNFα into the medium forebrain bundle of the rat leads to dopamine neuron cell loss in ventral mesencephalon (Carvey et al 2005). The toxic action has been suggested to be mediated via TNFR1 and data presented by Clarke et al indicate improved survival of transplanted fetal dopaminergic neurons by including TNFR1 antibody in the cell suspension to block TNFα (Clarke and Branton 2002).…”

Section: Discussionmentioning

confidence: 99%

Dual effects of TNFα on nerve fiber formation from ventral mesencephalic organotypic tissue cultures

Marschinke

Strömberg

2008

Brain Research

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Tumor necrosis factor alpha (TNFα) is toxic to dopamine neurons and increased levels of TNFα are observed in Parkinson's disease. Dopamine nerve fiber outgrowth in organotypic cultures of fetal ventral mesencephalon occurs in two waves. The early appearing nerve fibers are formed in the absence of astroglia, while migrating astrocytes guide the late appearing dopamine nerve fibers. TNFα (40 ng/ml) was added to the medium of organotypic ventral mesencephalic tissue cultures between days 4-7 or 11-14. The cultures were evaluated at days 7 or 19 to study effects of TNFα on both types of nerve fiber formation. Tyrosine hydroxylase (TH) -immunohistochemistry demonstrated that the number of cultures showing non-glial-guided TH-positive outgrowth was reduced compared to controls, when TNFα was added at day 4. By contrast, the glial-guided THpositive nerve fiber outgrowth and the astrocytic migration reached significantly longer distances by early TNFα treatment. Ki67-immunohistochemistry revealed that TNFα did not affect proliferation of astrocytes. Treatment with TNFα and antibodies against TNFα receptor 1 between days 4-7 revealed that the non-glial-guided TH-positive outgrowth reappeared. TNFα treatment between days 11-14 triggered neither the TH-positive glial-guided outgrowth, nor promoted the astrocytic migration to reach longer distances. The number of microglia was significantly increased after the late but not early TNFα treatment. In conclusion, TNFα is toxic for the non-glial dopaminergic nerve fiber outgrowth but stimulates the glial-guided outgrowth and the migration of astrocytes at an early time point. TNFα increased the number of microglia in VM tissue cultures after late but not after early treatment.

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“…Although direct injection of exogenous IL-1 into the rat brain has been reported to cause some loss of dopaminergic neurons (Carvey et al, 2005), studies on the effect of IL-b administration on normal neurons or healthy animals have not reported any evident neuronal loss. On the contrary, considerably greater tissue damage was observed when IL-1b was administered along with other cytokines into a healthy animal, suggesting a functional reinforcement in the action of these inflammatory factors (Downen et al, 1999).…”

Section: Potential Role Of Inflammasomes and Proinflammatory Cytokinementioning

confidence: 99%

Inflammasome signaling at the heart of central nervous system pathology

Chakraborty

Kaushik

Gupta

et al. 2010

J of Neuroscience Research

169

111

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Neuroinflammation is a complex innate response of neural tissue against harmful effects of diverse stimuli viz., pathogens, damaged cells and irritants within the Central Nervous System (CNS). Studies show that multiple inflammatory mediators including cytokines, chemokines and prostaglandins are elevated in the Cerebrospinal Fluid (CSF) and in post-mortem brain tissues of patients with history of neuroinflammatory conditions as well as neurodegenerative disorders like Alzheimer's disease, Parkinson's disease and Multiple Sclerosis. The innate immunity mediators in the brain, namely microglia and astrocytes, express certain Pattern Recognition Receptors (PRRs), which are always on 'high-alert' for pathogens or other inflammatory triggers and participate in the assembly and activation of the inflammasome. The inflammasome orchestrates the activation of the precursors of proinflammatory caspases, which in turn, cleave the precursor forms of interleukin-1beta, IL-18 and IL-33 into their active forms; the secretion of which leads to a potent inflammatory response, and/or influences the release of toxins from glial and endothelial cells. Altered expression of inflammasome mediators can either promote or inhibit neurodegenerative processes. Therefore, modulating the inflammasome machinery seems a better combat strategy than summarily suppressing all inflammation in most neuroinflammatory conditions. In the current review we have surveyed the identified triggers and pathways of inflammasome activation and the following events which ultimately accomplish the innate inflammatory response in the CNS, with a goal to provide an analytical insight into disease pathogenesis that might provide cues for devising novel therapeutic strategies.

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Intra-parenchymal injection of tumor necrosis factor-? and interleukin 1-? produces dopamine neuron loss in the rat

Cited by 73 publications

References 35 publications

Autologous transplants of Adipose-Derived Adult Stromal (ADAS) cells afford dopaminergic neuroprotection in a model of Parkinson's disease

Autologous transplants of Adipose-Derived Adult Stromal (ADAS) cells afford dopaminergic neuroprotection in a model of Parkinson's disease

Dual effects of TNFα on nerve fiber formation from ventral mesencephalic organotypic tissue cultures

Inflammasome signaling at the heart of central nervous system pathology

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