Dexamethasone protects against dopaminergic neurons damage in a mouse model of Parkinson's disease

Kurkowska‐Jastrzębska, Iwona; Litwin, Tomasz; Joniec, Ilona; Ciesielska, Agnieszka; Przybyłkowski, Adam; Członkowski, Andrzej; Członkowska, Anna

doi:10.1016/j.intimp.2004.05.006

Cited by 110 publications

(67 citation statements)

References 32 publications

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“…In vivo studies in mouse models have demonstrated that intraperitoneal injections of Dex may exert a neuroprotective effect towards injured neurons, but only in proper doses [54]. While higher doses of Dex may be toxic to neurons, a lower dose has proven to have a neuroprotective effect in those experiments.…”

Section: Resultsmentioning

confidence: 99%

Electrochemically controlled release of dexamethasone from conducting polymer polypyrrole coated electrode

Wadhwa

Lagenaur

Cui

2006

Journal of Controlled Release

456

393

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Chronic recordings from micromachined neural electrode arrays often fail a few weeks after implantation primarily due to the formation of an astro-glial sheath around the implant. We propose a drug delivery system, from conducting polymer (CP) coatings on the electrode sites, to modulate the inflammatory implant-host tissue reaction. In this study, polypyrrole (PPy) based coatings for electrically controlled and local delivery of the ionic form of an anti-inflammatory drug, dexamethasone (Dex), was investigated. The drug was incorporated in PPy via electropolymerization of pyrrole and released in PBS using cyclic voltammetry (CV). FTIR analysis of the surface showed the presence of Dex and polypyrrole on the coated electrode. The thickness of the coated film was estimated to be ~50 nm by ellipsometry. We were able to release 0.5 µg/cm 2 Dex in 1 CV cycle and upto 92% Dex after 30 CV cycles. In-vitro studies and immunocytochemistry on murine glial cells suggest that the released drug lowers the count of reactive astrocytes to the same extent as the added drug. In addition, the released drug is not toxic to neurons as seen by healthy neuronal viability in the released drug treated cells.

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Section: Resultsmentioning

confidence: 99%

Electrochemically controlled release of dexamethasone from conducting polymer polypyrrole coated electrode

Wadhwa

Lagenaur

Cui

2006

Journal of Controlled Release

456

393

View full text Add to dashboard Cite

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“…This drug had been shown to protect DA neurons in the in vivo MPTP model via a decrease of the inflammatory reaction of glial cells (Kurkowska-Jastrzebska et al 2004). We also observed complete protection from CM toxicity (Fig.…”

Section: Pharmacological Protection Of Neurons From Cytokine Toxicitymentioning

confidence: 99%

“…The causal role of astrocytes in disease has been probed by several pharmacological interventions (Kohutnicka et al 1998;Kurkowska-Jastrzebska et al 2004), and also genetic tools exist to deplete such cells from the brain (Mayo et al 2014), but the interpretation of such studies is difficult. The pathological and toxicological role of astrocytes may be highly model-specific, as they contribute to the metabolism of some toxicants (Schildknecht et al 2012) and they show a large plasticity, e.g., by taking the role of stem cells (Robel et al 2011).…”

Section: Introductionmentioning

confidence: 99%

Switching from astrocytic neuroprotection to neurodegeneration by cytokine stimulation

et al. 2016

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were involved in this neurodegeneration. The neurotoxicity-mediating effect of IMA was faithfully reproduced by human astrocytes. Moreover, glia-dependent toxicity was also observed, when IMA cultures were stimulated with CM, and the culture medium was transferred to neurons. Such neurotoxicity was prevented when astrocytes were treated by p38 kinase inhibitors or dexamethasone, whereas such compounds had no effect when added to neurons. Conversely, treatment of neurons with five different drugs, including resveratrol and CEP1347, prevented toxicity of astrocyte supernatants. Thus, the sequential IMA-LUHMES neuroinflammation model is suitable for separate profiling of both glial-directed and directly neuroprotective strategies. Moreover, direct evaluation in co-cultures of the same cells allows for testing of therapeutic effectiveness in more complex settings, in which astrocytes affect pharmacological properties of neurons.Keywords LUHMES · Astrocyte · p38 kinase · Neuroinflammation · Neuropharmacology Abstract Astrocytes, the largest cell population in the human brain, are powerful inflammatory effectors. Several studies have examined the interaction of activated astrocytes with neurons, but little is known yet about human neurotoxicity under such situations and about strategies of neuronal rescue. To address this question, immortalized murine astrocytes (IMA) were combined with human LUHMES neurons and stimulated with an inflammatory (TNF, IL-1) cytokine mix (CM). Neurotoxicity was studied both in co-cultures and in monocultures after transfer of conditioned medium from activated IMA. Interventions with >20 drugs were used to profile the model system. Control IMA supported neurons and protected them from neurotoxicants. Inflammatory activation reduced this protection, and prolonged exposure of co-cultures to CM triggered neurotoxicity. Neither the added cytokines nor the release of NO from astrocytes Liudmila Efremova and Petra Chovancova have contributed equally to this study.

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“…Chen and colleagues reported that caffeine restrained the MPTP-induced loss of DA neurons, leakage of Evan's blue and FITC-LA while decreasing expression of the TJ proteins ZO-1 and occludin in the striatum (72). Dexamethasone and indomethasin exerted neuroprotective effects on DA neurons by reducing the amount of infiltrated leukocytes in MPTP-treated SN as well as inhibition of glial activation (78,79). Our unpublished data also demonstrated that WIN55,212-2, a synthetic cannabinoid, inhibited not only microglial activation and ROS production (data not Shown) but also disruption of BBB and leukocyte infiltration in the MPTP model ( Fig.…”

Section: Neuroprotective Strategies For the Regulation Of Neuroinflammentioning

confidence: 99%

The role of neuroinflammation on the pathogenesis of Parkinson's disease

Chung¹,

Ko²,

Bok³

et al. 2010

BMB Reports

140

124

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Dexamethasone protects against dopaminergic neurons damage in a mouse model of Parkinson's disease

Cited by 110 publications

References 32 publications

Electrochemically controlled release of dexamethasone from conducting polymer polypyrrole coated electrode

Electrochemically controlled release of dexamethasone from conducting polymer polypyrrole coated electrode

Switching from astrocytic neuroprotection to neurodegeneration by cytokine stimulation

The role of neuroinflammation on the pathogenesis of Parkinson's disease

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