Naloxone Protects Rat Dopaminergic Neurons against Inflammatory Damage through Inhibition of Microglia Activation and Superoxide Generation
Abstract
Degeneration of dopaminergicrgic neurons in the substantia nigra of the brain is a hallmark of Parkinson's disease and inflammation and oxidative stress are closely associated with the pathogenesis of degenerative neurological disorders. Treatment of rat mesencephalic mixed neuron-glia cultures with lipopolysaccharide (LPS)-activated microglia, resident immune cells of the brain, to release proinflammatory and neurotoxic factors tumor necrosis factor-alpha, interleukin-1beta, nitric oxide, and superoxide and subsequently caused damage to midbrain neurons, including dopaminergic neurons. The LPS-induced degeneration of the midbrain neurons was significantly reduced by cotreatment with naloxone, an opioid receptor antagonist. This study focused on understanding the mechanism of action for the protective effect of naloxone on dopaminergic neurons because of relevance to Parkinson's disease. Both naloxone and its opioid receptor inactive stereoisomer (+)-naloxone protected the dopaminergic neurons with equal potency. Naloxone inhibited LPS-induced activation of microglia and release of proinflammatory factors, and inhibition of microglia generation of superoxide free radical best correlated with the neuroprotective effect of naloxone isomers. To further delineate the site of action, naloxone was found to partially inhibit the binding of [(3)H]LPS to cell membranes, whereas it failed to prevent damage to dopaminergic neurons by peroxynitrite, a product of nitric oxide and superoxide. These results suggest that naloxone at least in part interferes with the binding of LPS to cell membranes to inhibit microglia activation and protect dopaminergic neurons as well as other neurons in the midbrain cultures from inflammatory damage.
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Alternative anti-inflammatory drugs including dexamethasone, minocycline, naloxone are being or have been tested in preclinical and clinical trials for PD.
“Alternative drugs with anti-inflammatory properties, including dexamethasone, minocycline, naloxone, are going to be or have already been tested in preclinical and clinical trials.560–562”
From Role of neuroinflammation in neurodegeneration development (2023) · cites this paper as [562]
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BackgroundMethodInfluentialSelf-citationRole of Cdk5-Mediated Phosphorylation of Prx2 in MPTP Toxicity and Parkinson's Disease
Qu, D., Rashidian, J., Mount, M. P., Aleyasin, H., Parsanejad, M., Lira, A., Haque, E., Zhang, Y., Callaghan, S. M., Daigle, M., et al. (2007) · Neuron · doi:10.1016/j.neuron.2007.05.033 · Cited by 251 · see citing works
“Alternatively, for midbrain neuronal cultures, the whole midbrain, without meninges and blood vessels, was collected from embryos aged 13.5 days gestation and processed as above and as similarly described (Liu et al., 2000).”
BackgroundMethodInfluentialIravani, M. M., Kashefi, K., Mander, P., Rose, S., & Jenner, P. (2002) · Neuroscience · doi:10.1016/s0306-4522(01)00562-0 · Cited by 247 · see citing works
Regulating Factors for Microglial Activation.
Nakamura, Y. (2002) · Biological and Pharmaceutical Bulletin · doi:10.1248/bpb.25.945 · Cited by 241 · see citing works
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“Anti-inflammatory compounds, such as naloxane, minocycline and dexamethasone can reduce microglia activation and neuronal damage in different models of nigral degeneration (Liu et al., 2000; Lu et al., 2000; Tikka et al., 2001; Castano et al., 2002; Wu et al., 2002).”
BackgroundThe lipopolysaccharide Parkinson’s disease animal model: mechanistic studies and drug discovery
Dutta, G., Zhang, P., & Liu, B. (2008) · Fundamental & Clinical Pharmacology · doi:10.1111/j.1472-8206.2008.00616.x · Cited by 235 · see citing works
Self-citationFerrari, C. C., Pott Godoy, M. C., Tarelli, R., Chertoff, M., Depino, A. M., & Pitossi, F. J. (2006) · Neurobiology of Disease · doi:10.1016/j.nbd.2006.06.013 · Cited by 235 · see citing works
“…addition, several anti-inflammatory agents such as minocycline and naloxone that have been shown to ameliorate neurodegeneration in PD models also diminished IL-1β expression in those models (reviewed in Hald and Lotharius, 2005; Liu et al., 2000a,b; Sanchez-Pernaute et al., 2004; Wu et al., 2002).”
BackgroundReciprocal Interactions Between Microglia and Neurons: From Survival to Neuropathology
Polazzi, E., & Contestabile, A. (2002) · Reviews in the Neurosciences · doi:10.1515/revneuro.2002.13.3.221 · Cited by 232 · see citing works
Role of reactive oxygen species in LPS‐induced production of prostaglandin E2in microglia
Wang, T., Qin, L., Liu, B., Liu, Y., Wilson, B. C., Eling, T. E., Langenbach, R. I., Taniura, S., & Hong, J. (2004) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2003.02242.x · Cited by 218 · see citing works
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“The release of superoxide was determined by measuring the inhibition of reduction of cytochrome c by superoxide dismutase (SOD) as described previously (Liu et al., 2000).”
BackgroundMethodInfluentialSelf-citationFibromyalgia Symptoms Are Reduced by Low-Dose Naltrexone: A Pilot Study
Younger, J., & Mackey, S. (2009) · Pain Medicine · doi:10.1111/j.1526-4637.2009.00613.x · Cited by 216 · see citing works
“More recently, naltrexone (and its shorter acting cousin, naloxone) has also been found to attenuate the production of proinflammatory cytokines and neurotoxic superoxides via suppressive effects on central nervous system microglia cells [23–27].”
BackgroundQin, L., Li, G., Qian, X., Liu, Y., Wu, X., Liu, B., Hong, J., & Block, M. L. (2005) · Glia · doi:10.1002/glia.20225 · Cited by 210 · see citing works
“Primary enriched microglia cultures were prepared from the whole brains of two-day-old rat or mouse pups, using the previously described procedure (Liu et al., 2000).”
MethodSelf-citationYounger, J., Noor, N., McCue, R., & Mackey, S. (2013) · Arthritis & Rheumatism · doi:10.1002/art.37734 · Cited by 209 · see citing works
Liu, Y., Qin, L., Li, G., Zhang, W., An, L., Liu, B., & Hong, J. (2003) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.102.043166 · Cited by 205 · see citing works
“The neuroprotective effect of naloxone has been observed in both the in vitro and in vivo models of inflammation-mediated neurodegeneration (Lu et al., 2000; Liu et al., 2000a,b, 2002b).”
BackgroundInfluentialSelf-citationZhang, W., Wang, T., Qin, L., Gao, H., Wilson, B. C., Ali, S. F., Zhang, W., Hong, J., & Liu, B. (2004) · The FASEB Journal · doi:10.1096/fj.03-0983fje · Cited by 204 · see citing works
“Primary mesencephalic neuron-glia cultures were prepared from the brains of embryonic day 12/13 C57BL/6J mice (Jackson Laboratory), following our previously described protocol (30) with subsequent modifications (31).”
MethodSelf-citationMoon, M., Kim, H. G., Hwang, L., Seo, J.-H., Kim, S., Hwang, S., Kim, S., Lee, D., Chung, H., Oh, M. S., et al. (2009) · Neurotoxicity Research · doi:10.1007/s12640-009-9037-x · Cited by 203 · see citing works
“In fact, several agents have been found to be neuroprotective due to their ability to suppress the activation of microglia in various PD models (Liu et al. 2000; Wu et al. 2002; Breidert et al. 2002; Delgado and Ganea 2003; Liu et al. 2003).”
BackgroundTomás-Camardiel, M., Rite, I., Herrera, A. J., de Pablos, R. M., Cano, J., Machado, A., & Venero, J. L. (2004) · Neurobiology of Disease · doi:10.1016/j.nbd.2004.01.010 · Cited by 203 · see citing works
de Pablos, R. M., Herrera, A. J., Espinosa-Oliva, A. M., Sarmiento, M., Muñoz, M. F., Machado, A., & Venero, J. L. (2014) · Journal of Neuroinflammation · doi:10.1186/1742-2094-11-34 · Cited by 201 · see citing works
“The neurotoxic effect of LPS has been also observed in mesencephalic cell cultures [30-33].”
BackgroundGayle, D. A., Ling, Z., Tong, C. W., Landers, T. M., Lipton, J. W., & Carvey, P. M. (2002) · Developmental Brain Research · doi:10.1016/s0165-3806(01)00315-7 · Cited by 201 · see citing works
Lipopolysaccharide Animal Models for Parkinson's Disease
Liu, M., & Bing, G. (2011) · Parkinson s Disease · doi:10.4061/2011/327089 · Cited by 191 · see citing works
“For example, naloxone, an antagonist of opioid receptors, provided the dopaminergic neuroprotective e ff ects against LPS damage [32, 38, 53].”
Arimoto, T., & Bing, G. (2003) · Neurobiology of Disease · doi:10.1016/s0969-9961(02)00017-7 · Cited by 202 · see citing works
“Recently, a number of studies have shown that injection of LPS into the SN induced a selective dopaminergic neuronal loss (Castano et al., 1998; Herrera et al., 2000; Liu et al., 2000).”
BackgroundZhang, F., Shi, J., Zhou, H., Wilson, B. C., Hong, J., & Gao, H. (2010) · Molecular Pharmacology · doi:10.1124/mol.110.064535 · Cited by 189 · see citing works
“Using in vitro midbrain neuron-glia cocultures, we have demonstrated a critical role of proinflammatory factor release from activated microglia in DA neurotoxicity (Liu et al., 2000).”
BackgroundMethodInfluentialSelf-citationHa, S. K., Lee, P., Park, J. A., Oh, H. R., Lee, S., Park, J. H., Lee, E. H., Ryu, J. H., Lee, K. R., & Kim, S. Y. (2007) · Neurochemistry International · doi:10.1016/j.neuint.2007.10.005 · Cited by 187 · see citing works
“Naloxone reduces the neurotoxicity mediated by cytotoxic agents released from microglia in vitro and in vivo experiment (Liu et al., 2000a,b).”
BackgroundColler, J. K., & Hutchinson, M. R. (2012) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2012.01.008 · Cited by 186 · see citing works
“This TLR4 activity of (+)-naloxone (Hutchinson et al., 2008c) extends to the classical ligands of TLR4 with LPS-induced glial activation also blocked by (+)- naloxone (Liu et al., 2000b).”
BackgroundPeng, G.-S., Li, G., Tzeng, N., Chen, P.-S., Chuang, D., Hsu, Y., Yang, S., & Hong, J. (2004) · Molecular Brain Research · doi:10.1016/j.molbrainres.2004.10.021 · Cited by 170 · see citing works
Self-citationHaslund‐Vinding, J., McBean, G., Jaquet, V, & Vilhardt, F. (2017) · British Journal of Pharmacology · doi:10.1111/bph.13425 · Cited by 169 · see citing works
Liu, B., Jiang, J., Wilson, B. C., Du, L., Yang, S., Wang, J., Wu, G.-C., Cao, X.-D., & Hong, J. (2000) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(24)38877-9 · Cited by 167 · see citing works
“Using rat mesencephalic neuron-glia cultures, we have recently demonstrated that treatment of the cultures with the bacterial endotoxin LPS induced the activation of microglia that in turn produced large quantities of TNFa, IL-1b, NO, and superoxide free radicals (Liu et al., 2000).”
InfluentialSelf-citationGene–environment interactions: Key to unraveling the mystery of Parkinson's disease
Gao, H., & Hong, J. (2011) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2011.03.005 · Cited by 164 · see citing works
Self-citationSayyah, M., Javadpour, M., & Ghazi‐Khansari, M. (2003) · Neuroscience · doi:10.1016/j.neuroscience.2003.08.043 · Cited by 164 · see citing works
“001 compared with LPS (1 mg/kg) group. lus, which activates microglia to release the inflammatory mediators (Hetier et al., 1990; Lee et al., 1993; Liu et al., 2000a,b; Matoth et al., 2000; Turrin et al., 2001; Schuligoi et al., 2003).”
InfluentialThe Role of Microglia in Paraquat-Induced Dopaminergic Neurotoxicity
Wu, X.-F., Block, M. L., Zhang, W., Qin, L., Wilson, B. C., Zhang, W.-Q., Veronesi, B., & Hong, J. (2005) · Antioxidants and Redox Signaling · doi:10.1089/ars.2005.7.654 · Cited by 158 · see citing works
“2 demonstrates that only DA uptake was reduced significantly ( p < 0.01) by the addition of PQ to neuron-glia cultures, whereas GABA uptake remained unaffected ( p > 0.05).”
InfluentialSelf-citationRole of Endogenous Lipopolysaccharides in Neurological Disorders
Kalyan, M., Hediyal, T. A., Sonali, S., Vichitra, C., Sunanda, T., Praveenraj, S. S., Ray, B., Gorantla, V. R., Rungratanawanich, W., Mahalakshmi, A. M., et al. (2022) · Cells · doi:10.3390/cells11244038 · Cited by 160 · see citing works
“It causes microglial activation and the release of proinflammatory cytokines and neurotoxic factors such as IL-1β, TNF-α, prostaglandins, superoxide, and NO that damage dopaminergic neurons [49] via mitochondrial dysfunction and apoptosis [85,86].”
BackgroundLi, Q., Xu, Z., Zhang, W., Wilson, B. C., Hong, J., & Flood, P. M. (2007) · Journal of Neuroinflammation · doi:10.1186/1742-2094-4-23 · Cited by 154 · see citing works
“Neuron-glia cultures were prepared from the ventral mesencephalic tissues of embryonic day 14–15 rats or day 13– 14 mice, as described previously [18].”
BackgroundMethodResultInfluentialSelf-citationNeuroprotective effect of nicotine on dopaminergic neurons by anti‐inflammatory action
Park, H.-J., Lee, P. H., Ahn, Y. W., Choi, Y. J., Lee, G., Lee, D., Chung, E. S., & Jin, B. K. (2007) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2007.05636.x · Cited by 153 · see citing works
Chondroitin Sulfate Proteoglycans in the Nervous System: Inhibitors to Repair
Siebert, J. R., Conta, A. C., & Osterhout, D. J. (2014) · BioMed Research International · doi:10.1155/2014/845323 · Cited by 151 · see citing works
“These experiments revealed a significant increase in microglia activation throughout this subcortical area preceding marked neuronal death [59].”
BackgroundEvidence of Inflammatory System Involvement in Parkinson’s Disease
Chao, Y., Wong, S. C., & Tan, E. K. (2014) · BioMed Research International · doi:10.1155/2014/308654 · Cited by 150 · see citing works
Chen, H.-Q., Jin, Z., Wang, X., Xu, X., Deng, L., & Zhao, J.-W. (2008) · Neuroscience Letters · doi:10.1016/j.neulet.2008.10.046 · Cited by 150 · see citing works
“Rat microglia-enriched cultures were prepared from whole brains of one-day-old Sprague-Dawley rats as described previously [9].”
InfluentialArimoto, T., Choi, D., Lü, X., Liu, M., Nguyen, X. V., Zheng, N., Stewart, C. A., Kim, H., & Bing, G. (2006) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2006.04.011 · Cited by 149 · see citing works
Awareness and current knowledge of Parkinson’s disease: a neurodegenerative disorder
Khan, A. U., Akram, M., Daniyal, M., & Zainab, R. (2018) · International Journal of Neuroscience · doi:10.1080/00207454.2018.1486837 · Cited by 145 · see citing works
“Independent determinants for the progression of apathy include memory loss at baseline, axial impairment and a more quick decline in speech [245].”
BackgroundPatten, D. K., Schultz, B. G., & Berlau, D. J. (2018) · Pharmacotherapy The Journal of Human Pharmacology and Drug Therapy · doi:10.1002/phar.2086 · Cited by 136 · see citing works
“One rat study demonstrated that only a small dose of naloxone is needed to impact some of the functions of glial cells and macrophages.(14) A different in vitro study suggests that this may also be the case with naltrexone, although more weakly than naloxone.”
BackgroundMolecular consequences of activated microglia in the brain: overactivation induces apoptosis
Liu, B., Wang, K., Gao, H.-M., Mandavilli, B., Wang, J.-Y., & Hong, J.-S. (2001) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2001.t01-1-00216.x · Cited by 286 · see citing works
Self-citationLi, F.-Q., Wang, T., Pei, Z., Liu, B., & Hong, J. (2004) · Journal of Neural Transmission · doi:10.1007/s00702-004-0213-0 · Cited by 135 · see citing works
Self-citationTian, Y.-Y., An, L., Jiang, L., Duan, Y.-L., Chen, J., & Jiang, B. (2006) · Life Sciences · doi:10.1016/j.lfs.2006.09.010 · Cited by 133 · see citing works
“Injection of bacterial lipopolysaccharide (LPS) into rat SN and the ensuing microglial activation has been shown to induce dopaminergic neurodegeneration (Liu et al., 2000b; Iravani et al., 2002).”
MethodWang, T., Liu, B., Zhang, W., Wilson, B. C., & Hong, J. (2004) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.103.059683 · Cited by 133 · see citing works
“Reagents.”
BackgroundMethodInfluentialSelf-citationImamura, K., Hishikawa, N., Ono, K., Suzuki, H., Sawada, M., Nagatsu, T., Yoshida, M., & Hashizume, Y. (2004) · Acta Neuropathologica · doi:10.1007/s00401-004-0919-y · Cited by 131 · see citing works
“Many studies indicate the vulnerability of neurons to the potential toxicity of microglia, which produces neurotoxic substances including superoxide anion, nitric oxide (NO), glutamate, and pro-inflammatory cytokines [8, 9, 22, 23, 26, 35, 37, 40, 47].”
BackgroundLi, Q., Wei, S., Zhang, D., Hu, X., Xu, Z., Wilson, B. C., Benna, J. E., Hong, J., & Flood, P. M. (2008) · The Journal of Immunology · doi:10.4049/jimmunol.181.1.660 · Cited by 128 · see citing works
“Neuron-glia cultures were prepared from the ventral mesencephalic tissues of embryonic day 14–15 rats or day 13–14 mice, as described previously (31, 32).”
MethodSelf-citationFluoxetine protects neurons against microglial activation-mediated neurotoxicity
Zhang, F., Zhou, H., Wilson, B. C., Shi, J.-S., Hong, J.-S., & Gao, H.-M. (2012) · Parkinsonism & Related Disorders · doi:10.1016/s1353-8020(11)70066-9 · Cited by 123 · see citing works
“Rat primary neuron-glia, neuron-astrocyte, neuron-microglia and neuron-enriched cultures were prepared from the ventral mesencephalic tissues of embryonic day 14–15 rats as described previously [10, 11].”
MethodSelf-citationCurrent and Emerging Pharmacotherapy for Fibromyalgia
Tzadok, R., & Ablin, J. N. (2020) · Pain Research and Management · doi:10.1155/2020/6541798 · Cited by 122 · see citing works
“Inhibition of microglial activation by naltrexone or naloxone therefore has an anti-inflammatory effect through the decrease in production of neurotoxic chemicals [66, 67], which is suggested to contribute to its analgesic effect [25].”
BackgroundSelley, M. L. (2005) · Brain Research · doi:10.1016/j.brainres.2004.02.083 · Cited by 122 · see citing works
Arai, H., Furuya, T., Yasuda, T., Miura, M., Mizuno, Y., & Mochizuki, H. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m407328200 · Cited by 122 · see citing works
Li, Q., Wu, H., Chen, S., Zhang, D., Ali, S. F., Peterson, L. J., Wilson, B. C., Lu, R., Hong, J., & Flood, P. M. (2011) · The Journal of Immunology · doi:10.4049/jimmunol.1002449 · Cited by 118 · see citing works
“Neuron-glia cultures were prepared from the ventral mesencephalic tissues of embryonic day 14–15 rats or day 13–14 mice, as described previously (21, 22).”
MethodSelf-citationUpdates on immunity and inflammation in Parkinson disease pathology
Joshi, N., & Singh, S. (2017) · Journal of Neuroscience Research · doi:10.1002/jnr.24185 · Cited by 118 · see citing works
Wang, S., Hu, L., Gao, X., Guo, H. W., & Fan, G. (2010) · Neurochemical Research · doi:10.1007/s11064-010-0151-1 · Cited by 117 · see citing works
Shih, Y.-T., Chen, P. S., Wu, C.-H., Tseng, Y.-T., Wu, Y., & Lo, Y. (2010) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2010.07.017 · Cited by 116 · see citing works
“Primary cortical neuron cultureswere prepared from gestation day 15–16 rat embryos and cultured as described previously [39].”
MethodTomás‐Camardiel, M., Venero, J. L., Herrera, A. J., de Pablos, R. M., Pintor‐Toro, J. A., Machado, A., & Cano, J. (2005) · Journal of Neuroscience Research · doi:10.1002/jnr.20443 · Cited by 116 · see citing works
“Statistical significance (Student’s t-test): *P < 0.05; **P < 0.01 comparing the E2-treated and untreated animals for every time point. death of dopaminergic neurons (Castaño et al., 1998; Liu et al., 2000; Lu et al., 2000; Gao et al., 2002).”
BackgroundInfluentialMicroglial regulation of immunological and neuroprotective functions of astroglia
Chen, S., Oyarzabal, E. A., Sung, Y.-F., Chu, C., Wang, Q., Chen, S.-L., Lu, R., & Hong, J.-S. (2014) · Glia · doi:10.1002/glia.22738 · Cited by 115 · see citing works
“NO was assessed by measuring nitrite in 50 mL of supernatants using Griess reagent as described previously (Liu et al., 2000).”
MethodSelf-citationMcCoy, M. K., Ruhn, K. A., Martinez, T. N., McAlpine, F. E., Blesch, A., & Tansey, M. G. (2008) · Molecular Therapy · doi:10.1038/mt.2008.146 · Cited by 115 · see citing works
Li, Q., Block, M. L., Wei, S., Lin, C., Reece, J. M., Pang, H., Wilson, B. C., Hong, J., & Flood, P. M. (2006) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.106.106351 · Cited by 110 · see citing works
Self-citationNeuroprotection of Scutellarin is mediated by inhibition of microglial inflammatory activation
Wang, S., Wang, H., Guo, H. W., Kang, L., Gao, X., & Hu, L. (2011) · Neuroscience · doi:10.1016/j.neuroscience.2011.04.005 · Cited by 107 · see citing works
Pei, Z., Pang, H., Qian, L., Yang, S., Wang, T., Zhang, W., Wu, X., Dallas, S., Wilson, B., Reece, J. M., et al. (2007) · Glia · doi:10.1002/glia.20545 · Cited by 105 · see citing works
“Primary enriched microglia cultures were prepared from the whole brains of day-old mouse pups (MAC1, MAC1, TLR4, TLR4, PHOX, and PHOX) using the procedure described previously (Liu et al., 2000).”
MethodSelf-citationIn vitro model of glial scarring around neuroelectrodes chronically implanted in the CNS
Polikov, V. S., Block, M. L., Fellous, J., Hong, J., & Reichert, W. M. (2006) · Biomaterials · doi:10.1016/j.biomaterials.2006.06.018 · Cited by 104 · see citing works
Self-citationJeong, H., Jou, I., & Joe, E.-H. (2010) · Experimental & Molecular Medicine · doi:10.3858/emm.2010.42.12.085 · Cited by 101 · see citing works
“Cultured microglia challenged with LPS and interferon-γ produce neurotoxic inflammatory mediators including inducible nitric oxide synthase (iNOS) (Liu et al., 2000; Possel et al., 2000; Min et al., 2006), whereas microglia activated in vivo by brain injury and/or LPS injection synthesize very…”
Herrera, A. J., Tomás‐Camardiel, M., Venero, J. L., Cano, J., & Machado, A. (2004) · Journal of Neural Transmission · doi:10.1007/s00702-004-0121-3 · Cited by 103 · see citing works
“These and other microglial factors could contribute significantly to dopaminergic degeneration (Liu et al., 2000; Gao et al., 2002).”
Mathieu, P., Battista, D., Depino, A. M., Roca, V., Graciarena, M., & Pitossi, F. J. (2009) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2009.06548.x · Cited by 104 · see citing works
“…the substantia nigra are particularly susceptible to microglial-mediated toxicity in vitro and in vivo (Castano et al. 1998, 2002; Kim et al. 2000; Liu et al. 2000) and this effect could be reversed by the administration of anti-inflammatory drugs (Liu et al. 2000; Castano et al. 2002;…”
Background
- Authors
- Liu, B., Du, L., & Hong, J.-S.
- Affiliations
- National Institutes of Health (US)
- National Institute of Environmental Health Sciences (US)
- Corresponding author
- Liu, Bin
- Venue
- The Journal of Pharmacology and Experimental Therapeutics
- Publisher
- Elsevier BV
- Published
- 2000-04
- Volume
- 293
- Issue
- 2
- Pages
- 607-617
- ISSN
- 0022-3565 (ISSN-L)
- OpenAlex
- W1891696008
- Cited by
- 347
- References
- 43
- Citations by year
- 2026: 4 · 2025: 6 · 2024: 4 · 2023: 11 · 2022: 11 · 2021: 10 · 2020: 5 · 2019: 2 · 2018: 7 · 2017: 12 · 2016: 10 · 2015: 16 · 2014: 11 · 2013: 13 · 2012: 26
- FWCI
- 8.42
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Pharmacology and Experimental Therapeutics (publishedVersion)
- PubMed (publishedVersion)
- PubMed
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nuclear Receptors and Signaling
- Keywords
- naloxone, dopaminergic neurons, Parkinson's disease, microglial activation, lipopolysaccharide, neuroinflammation, oxidative stress, superoxide, neuroprotection, substantia nigra, opioid antagonists, peroxynitrite, nitric oxide, inflammatory cytokines
- MeSH terms
- Animals, Cells, Cultured, Dopamine, Immunohistochemistry, Inflammation, Interleukin-1, Lipopolysaccharides, Mesencephalon, Naloxone, Narcotic Antagonists, Neurons, Nitrates, Nitrites, Rats, Inbred F344, Stereoisomerism, Substantia Nigra, Superoxides, Tumor Necrosis Factor-alpha, Tyrosine 3-Monooxygenase, Oxidants, Microglia, Mitogen-Activated Protein Kinases, Mitogen-Activated Protein Kinase 3, Rats
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