Determining the neuroprotective effects of dextromethorphan in lipopolysaccharide‑stimulated BV2 microglia

  • Authors:
    • Wenjing Cheng
    • Yunhong Li
    • Xiaolin Hou
    • Bin Bai
    • Fan  Li
    • Feijia  Ding
    • Jiao Ma
    • Nan Zhang
    • Ying Shen
    • Yin Wang
  • View Affiliations

  • Published online on: October 27, 2014
  • Pages: 1132-1138
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Microglial activation has been recognized as being vital in the pathogenesis of several neurodegenerative disorders. Therefore, the identification of therapeutic drugs to prevent microglial activation and thus protect against inflammation‑mediated neuronal injury, is required. In the present study, dextromethorphan (DM), a compound widely used in antitussive remedies that has been demonstrated to possess neuroprotective effects, was shown to reduce proinflammatory mediator production in lipopolysaccharide (LPS)‑stimulated BV2 mouse microglial cells. Western blot analysis revealed that DM markedly suppressed the activation of nuclear factor‑κB (NFκB), caspase‑3 signaling and the expression of another inflammation‑inducing factor, heat shock protein 60 (HSP60) and heat shock factor‑1, induced by LPS in BV2 cells. Results from ELISA assay demonstrated that DM reduced the release of HSP60, nitric oxide (NO), inducible NO synthase, tumor necrosis factor‑α, interleukin (IL)‑1β and IL‑6 induced by LPS in BV2 microglia. These results were confirmed by immunofluorescence, suggesting that DM may exert a neuroprotective and anti‑inflammatory effect by inhibiting microglial activation through the HSP60‑NFκB signaling pathway. Therefore, DM may offer substantial therapeutic benefits in the treatment of neurodegenerative diseases that are accompanied by microglial activation.


Microglial cells, resident brain macrophages of the central nervous system (CNS), are pivotal in the pathogenesis of several neurodegenerative diseases (1). Microglia are activated in response to stress, and are involved in innate and adaptive immune responses by inducing the production of various pro-inflammatory mediators, including nitric oxide (NO), inducible NO synthase (iNOS), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), IL-6, nuclear factor-κB (NFκB), caspase-3 and heat shock protein (HSP) 60 (26), all of which contribute to neurodegeneration (7,8). A number of microglia-targeted pharmacotherapies, such as protein kinase C inhibitors and microglia-inhibiting factors, have been proposed to suppress microglial activation and promote neuronal survival in vivo (911). However, the inability of these drugs to penetrate the blood-brain barrier and the complexity of current pharmacological agents, as well as the possible side effects, has halted long-term clinical use in the treatment and prevention of diseases of the CNS (12).

Dextromethorphan (DM), a derivative of morphinan, is one of the most widely used non-opioid cough suppressants, acting as the active ingredient in numerous antitussive formulations (13). As an antitussive, DM is superior to opioids used at antitussive doses in that DM lacks any gastrointestinal side effects, such as constipation, and produces a lower degree of depression of the CNS. DM is rapidly absorbed from the gastrointestinal tract, where it enters the bloodstream and crosses the blood-brain barrier (14). The anticonvulsant and neuroprotective properties of DM have been demonstrated, and treatment with DM has been shown to improve the cerebrovascular and functional consequences of global cerebral ischemia (14). However, the mechanisms underlying the neuroprotective effects of DM remain poorly understood.

Previous studies have demonstrated that naloxone, another analogue of morphinan, protects against lipopolysaccharide (LPS)-induced neurotoxicity in vitro and in vivo through the inhibition of the release of proinflammatory factors and free radicals (1518). DM is structurally similar to naloxone and has been shown to protect against LPS-induced dopamine neurodegeneration in mixed neuron-glia coculture through the inhibition of microglial overactivation, and the subsequent reduction in the levels of proinflammatory cytokines, free radicals and reactive oxygen species (19). In the present study, the DeltaVision Elite microscopy imaging system was used to analyze the effects of DM on the production of proinflammatory mediators.

Materials and methods


The following reagents were used in this study: DM and LPS (Sigma-Aldrich, St. Louis, MO, USA); rabbit monoclonal antibodies against β-actin and NF-κB p65 (Abcam, Cambridge, MA, USA); mouse monoclonal anti-HSP60 and anti-heat shock factor 1 (HSF1) antibodies (Stressgen®, San Diego, CA, USA; Enzo Life Sciences, Inc., Farmingdale, NY, USA); rabbit polyclonal anti-caspase-3 antibody (Cell Signaling Technology, Inc., Beverly, MA, USA); proteinase inhibitor cocktails (Merck Chemicals, Whitehouse Station, NJ, USA); IL-6, IL-1β and TNF-α ELISA kits (eBioscience, San Diego, CA, USA); bicinchoninic acid (BCA) and enhanced chemiluminescence (ECL) kits (Pierce Biotechnology, Inc., Rockford, IL, USA); Dulbecco’s modified Eagle’s medium (DMEM) and fetal bovine serum (FBS; Gibco-BRL, Grand Island, NY, USA); Griess reagent and iNOS kits (Nanjing Jiancheng Bioengineering Institute, Nanjing, China); Cell Counting kit-8 (CCK-8; Beyotime Biotech, Jiangsu, China); and fluorescein isothiocyanate (FITC)-conjugated Affinipure goat anti-rabbit and tetramethylrhodamine (TRITC)-conjugated Affinipure goat anti-mouse antibodies (Abcam). All additional materials were purchased from ZSGB-BIO (Beijing, China), unless otherwise stated.

Microglial cell culture

BV2 mouse microglial cells (Shanghai Cell Bank, Shanghai, China) were cultured in DMEM supplemented with 10% FBS, penicillin (100 units/ml) and streptomycin (100 g/ml). The cultures were maintained at 37°C in a humidified incubator with 95% O2 and 5% CO2. The cells were treated with 1 μg/ml LPS for 30 min, followed by administration of 10, 25, 50, 80 or 100 μM DM (dissolved in PBS) for 24 h.

Cell viability assay

Cell viability was measured using a CCK-8 assay. BV2 cells (5×104 cells in 100 μl/well) were seeded in 96-well plates. CCK-8 solution (10 μl) was added to each well and the cultures were incubated at 37°C for 90 min. The absorbance at 450 nm was measured using a SmartSpec Plus Spectrophotometer (Bio-Rad, Beijing, China). The results are plotted as the means ± standard deviation (SD) of three separate experiments with four determinations per experiment for each experimental condition. The cell survival ratio was calculated, normalizing the results to the control group (without LPS+DM).


The levels of IL-6, IL-1β, HSP60 and TNF-α present in the culture medium, were quantified according to the manufacturer’s instructions for the respective ELISA kits. The absorbance was determined at 450 nm using a Model 680 microplate reader (Bio-Rad, Beijing, China).

Western blot analysis

Western blotting was performed according to a standard method. Briefly, BV2 cells were washed with PBS three times and lyzed in radioimmunoprecipitation assay buffer. The protein concentration was determined using the BCA kit according to the manufacturer’s instructions. Equal quantities of each protein sample were separated by SDS-PAGE and then transferred to a polyvinylidene difluoride membrane. The membranes were blocked with 5% milk powder and incubated with the respective primary antibodies (anti-P65 1;1,000; anti-caspase, 1:1,000; anti-HSP60, 1:1,000; anti-HSF-1, 1:200; and anti-β-actin, 1:5,000) in Tris-buffered saline with Tween-20 (TBST) overnight at 4°C. Subsequent to rinsing in milk-TBST, the blots were incubated with horseradish peroxidase-conjugated secondary antibodies (1:5,000). The target proteins were detected by using the ECL detection system and X-ray films.


BV2 cells (5×104 cells in 100 μl/well) were seeded on coverslips in 24-well plates. Following 24 h incubation, the cells were treated with LPS (1 μg/ml) for 1 h and then incubated with the indicated concentrations of DM for 24 h. Subsequently, the cells were washed twice with PBS, fixed with 4% paraformaldehyde in PBS for 15 min, washed three times with PBS and then permeabilized with 0.5% Triton X-100 in PBS for 20 min. The cells were again washed three times with PBS and blocked with 5% bovine serum albumin for 1 h at 37°C. Following blocking, the cells were incubated with primary antibodies (anti-P65 1;100; anti-caspase, 1:100; anti-HSP60, 1:200; anti-HSF-1, 1:50; and anti-iNOS, 1:100) in PBS overnight at 4°C, then rinsed with PBS, and incubated with the FITC- and TRITC-conjugated secondary antibodies (1:1,000) for 1 h at 37°C. The cells were then washed with PBS, stained with DAPI and then mounted. Images were captured at magnification, ×400 using a DeltaVision Elite microscopy imaging system (Applied Precision; GE Healthcare, Issaquah, WA, USA).


Statistical differences were determined using a one-way analysis of variance test. P<0.05 was considered to indicate a statistically significance difference. The data represent the means ± standard error of the mean.


DM promotes the viability of BV2 microglia

To determine whether DM exerts an effect on the viability of LPS-stimulated BV2 cells, a CCK-8 assay was performed. The results demonstrated that the microglia group treated with 10–100 μM DM for 24 h exhibited significantly increased cell viability following LPS stimulation, as compared with the group treated with LPS alone (Fig. 1). The cells treated with 10 μM DM exhibited the maximal viability, as compared with the other concentrations, thus 10 μM was selected for subsequent experiments. The results indicated that DM may exert a positive effect on the viability of LPS-stimulated BV2 microglia.

DM inhibits NFκB and caspase-3 expression

NFκB regulates the expression of numerous proinflammatory factors and caspase-3 is an important protein in the NFκB signaling pathway. Inhibition of caspase-3 prevents the neuronal loss induced by activated microglia in brain diseases. Therefore, the effects of DM on NFκB and caspase-3 expression levels in LPS-stimulated BV2 microglia were investigated using western blotting. The levels of the p65 subunit of NFκB were significantly increased following LPS treatment, as compared with the control (P<0.05), but were markedly inhibited by DM, as compared with LPS treatment alone (P<0.05; Fig. 2A). Subsequent to LPS stimulation, caspase-3 expression was found to be significantly suppressed following DM treatment, as compared with LPS treatment only (P<0.05; Fig. 2B).

DM inhibits HSP60 protein expression and release in LPS-stimulated BV2 microglia

The levels of HSP60 expression and release were detected in activated BV2 cells. The western blotting results demonstrated that LPS significantly enhanced HSP60 expression levels, as compared with those of the control group (P<0.05), but DM significantly inhibited this increase, as compared with LPS treatment alone (P<0.05; Fig. 3A). HSF-1 has been shown to bind with the heat shock element on the HSP60 promoter to regulate HSP60 gene expression (20). Therefore, the HSF-1 expression levels were analyzed and were found to be significantly upregulated by LPS (P<0.05), but significantly downregulated by additional DM treatment (P<0.05). This indicated that HSP60 expression was induced by HSF-1 (Fig. 3B). HSP60 has been reported to translocate extracellularly upon stress to exert injury effects (21). The ELISA results demonstrated that HSP60 was released into the culture medium upon LPS-mediated activation of BV2, but the increased expression levels of extracellular HSP60 was significantly suppressed by the addition of DM (P<0.05; Fig. 3C).

DM inhibits proinflammatory factor production

ELISA assay was used to determine whether DM suppresses the release of proinflammatory factors, including NO, iNOS, TNF-α, IL-1β and IL-6 in LPS-stimulated BV2 cells. As shown in Fig. 4, 24 h LPS treatment of BV2 cells resulted in significant increases in the levels of the investigated proinflammatory factors in the culture media, as compared with the control (all P<0.05). However, additional DM treatment significantly reduced the release of all proinflammatory factors, as compared with LPS treatment alone (P<0.05). These results indicated that DM effectively suppressed the production of neurotoxic factors in overactivated microglia.


To confirm the results from traditional molecular techniques (western blotting and ELISA), immunofluorescence experiments were conducted. The staining patterns of protein localization using anti-HSP60, HSF-1, NFκB, caspase-3 and iNOS antibodies in LPS- and LPS+DM-treated cells were markedly different. The fluorescence intensities with those antibodies were markedly higher in the LPS group as compared with those in the DM group (Fig. 5A). The statistical analysis is shown in Fig. 5B and is consistent with the findings from the western blotting and ELISA. From these data, DM may be considered to effectively inhibit HSP60, HSF-1, NF-κB, caspase-3 and iNOS expression in LPS-stimulated microglia.


In the present study, treatment with 10 μM DM was demonstrated to effectively inhibit LPS-induced activation of microglia. DM reduced the expression levels of NFκB, caspase-3, HSP60, HSF-1 and iNOS in microglia, and effectively suppressed the release into the culture medium of HSP60, NO and several proinflammatory cytokines, including TNF-α, IL-6 and IL-1β, in microglia stimulated by LPS. Therefore, the data suggest that DM may be a useful therapeutic agent in the treatment of inflammatory diseases.

The activation of microglia is important in neural parenchymal defence against infectious diseases, as well as inflammation, trauma, ischaemia, brain tumors and neurodegeneration (22). The activated microglia secrete various proinflammatory and neurotoxic factors that are hypothesized to induce neurodegeneration (23). Therefore, the identification of novel strategies to reduce microglial overactivation is of therapeutic importance, and the inhibition of proinflammatory enzymes and cytokines may be an effective therapeutic approach against these neurodegenerative disorders. Previous studies have investigated the neuroprotective effects of several substances, including polysaccharides from Lycium barbarum (11), curcumin (24), fucoidan (25) and naloxone (unpublished data). The present study suggests that DM is also a potential therapeutic tool.

Numerous studies have reported that DM exerts neuroprotective effects (2628). DM is considered to be an antagonist of the N-methyl-D-aspartate (NMDA) receptor complex. Therefore the mechanism responsible for the neuroprotective activity of DM has been hypothesized to occur through antagonistic effects on the NMDA receptor (29). However, explaining the numerous observed beneficial effects becomes difficult due to the identification of high (nanomolar) and low (micromolar) affinity binding sites for DM in the CNS (30,31). In the present study, the neuroprotective effects of DM in the inflammation-mediated neurodegenerative disorders were found to have been most likely mediated by the inhibition of LPS-induced microglial activation and the suppression of neurotoxic factor production, but not by glutamate-mediated excitatory neurotoxicity.

The activation of NFκB is considered to be pivotal in the inflammatory response resulting from microglial activation. NFκB is a multifunctional transcription factor and is an important target in controlling inflammation, as the transcription of numerous proinflammatory molecules depends on the activation of NFκB (32,33). Therefore, several anti-inflammatory therapies have aimed to inhibit NFκB activity in LPS models or inflammatory diseases (34). Caspase-3 is crucial in cell death and CNS inflammation (35). LPS-stimulated microglia have been demonstrated to be non-toxic to neighboring neurons when caspase-3/7 is inhibited (36). The activation of NFκB by caspase-3 is also critical in inflammation. Thus, in the present study, the effects of DM on NFκB and caspase-3 expression levels were detected. The results demonstrated that DM treatment following LPS stimulation markedly inhibited caspase-3 and the NFκB downstream mediator p65, suggesting that the anti-inflammatory effects of DM may be a result of inhibition of the NFκB signaling pathway.

HSP60 is primarily considered to be a mitochondrial protein, but may translocate to the plasma membrane, even being released extracellularly upon stress, which is a process that has been demonstrated to be induced by the NFκB-p65 cascade (21). Extracellular HSP60 may become toxic by targeting self-reactive T cells in inflammatory diseases (37). HSP60 gene expression is regulated by the corresponding transcription factor, HSF-1, which binds to the HSP60 gene promoter. NFκB has also been shown to initiate transcription of the HSP60 stress gene, which elicits a potent proinflammatory response in innate immune cells (38). TNF-α is a mediator of NFκB signaling and induces an increase in the expression levels of HSP60, which has been shown to be reversed by p65 inhibition (38). Therefore, in the present study, HSP60 expression in BV2 cells and extracellular release, as well as TNF-α levels in the culture medium were measured, following NFκB activation by LPS. The results reveal that DM suppressed HSP60 expression and release, and also reduced extracellular TNF-α levels.

Microglial activation is widely known to produce proinflammatory cytokines, NO and iNOS. This was confirmed in the present study by measuring the levels of IL-1β, IL-6, NO and iNOS in the culture medium of BV2 cells stimulated by LPS. The iNOS gene is under the transcriptional control of various inflammatory mediators, including cytokines and LPS. NO, a product of iNOS, has been found to be important as a signaling molecule in a number of areas of the body, as well as acting as a cytotoxic or regulatory effector molecule of the innate immune response (39). However, in the present study, following DM treatment, IL-1β, IL-6, NO and iNOS expression levels were markedly inhibited.

Combined with results from previous studies, the findings from the present study indicate that DM may exert neuroprotective action through the inhibition of the NFκB signaling pathway to prevent the overactivation of microglia.


This study was supported by the National Natural Science Foundation of China (grant nos. 31060140 and 31260243), the Project-sponsored by SRF for ROCS and State Education Ministry. Additional funding was provided to Dr Yin Wang by the Program for New Century Excellent Talents in University.



Block ML, Zecca L and Hong JS: Microglia-mediated neurotoxicity: uncovering the molecular mechanisms. Nature Rev Neurosci. 8:57–69. 2007. View Article : Google Scholar


Hanisch UK and Kettenmann H: Microglia: active sensor and versatile effector cells in the normal and pathologic brain. Nat Neurosci. 10:1387–1394. 2007. View Article : Google Scholar : PubMed/NCBI


Gehrmann J, Matsumoto Y and Kreutzberg GW: Microglia: intrinsic immuneffector cell of the brain. Brain Res Rev. 20:269–287. 1995. View Article : Google Scholar : PubMed/NCBI


Innamorato NG, Lastres-Becker I and Cuadrado A: Role of microglial redox balance in modulation of neuroinflammation. Curr Opin Neurol. 22:308–314. 2009. View Article : Google Scholar : PubMed/NCBI


Lynch MA: The multifaceted profile of activated microglia. Mol Neurobiol. 40:139–156. 2009. View Article : Google Scholar : PubMed/NCBI


Li YH, Teng P, Wang Y, et al: Expression and regulation of HSP60 in activated microglia cells. J Ningxia Med Coll. 8:712–714. 2011.


Zhang D, Sun L, Zhu H, et al: Microglial LOX-1 reacts with extracellular HSP60 to bridge neuroinflammation and neurotoxicity. Neurochem Int. 61:1021–1035. 2012. View Article : Google Scholar : PubMed/NCBI


Lehnardt S, Schott E, Trimbuch T, et al: A vicious cycle involving release of heat shock protein 60 from injured cells and activation of toll-like receptor 4 mediates neurodegeneration in the CNS. J Neurosci. 28:2320–2331. 2008. View Article : Google Scholar : PubMed/NCBI


Thanos S, Mey J and Wild M: Treatment of the adult retina with microglia-suppressing factors retards axotomy-induced neuronal degradation and enhances axonal regeneration in vivo and in vitro. J Neurosci. 13:455–466. 1993.PubMed/NCBI


Thanos S: The relationship of microglial cells to dying neurons during natural neuronal cell death and axotomy-induced degeneration of the rat retina. Eur J Neurosci. 3:1189–1207. 1991. View Article : Google Scholar : PubMed/NCBI


Teng P, Li YH, Cheng WJ, et al: Neuroprotective effects of Lycium barbarum polysaccharides in lipopolysaccharide-induced BV2 microglia cells. Mol Med Rep. 7:1977–1981. 2013.PubMed/NCBI


Rangarajan P, Eng-Ang L and Dheen ST: Potential drugs targeting microglia: current knowledge and future prospects. CNS Neurol Disord Drug Targets. 12:799–806. 2013. View Article : Google Scholar : PubMed/NCBI


Shin EJ, Bach JH, Lee SY, Kim JM, Lee JJ, Hong JS, et al: Neuropsychotoxic and neuroprotective potentials of dextromethorphan and its analogs. J Pharmacol Sci. 116:137–148. 2011. View Article : Google Scholar : PubMed/NCBI


Mousavi SA, Saadatnia M, Khorvash F, Hoseini T and Sariaslani P: Evaluation of the neuroprotective effect of dextromethorphan in the acute phase of ischaemic stroke. Arch Med Sci. 7:465–469. 2011. View Article : Google Scholar


Liu B, Du L and Hong JS: Naloxone protects rat dopaminergic neurons against inflammatory damage through inhibition of microglia activation and superoxide generation. J Pharmacol Exp Ther. 293:607–617. 2000.PubMed/NCBI


Liu Y, Qin L, Wilson BC, et al: Inhibition by naloxone stereoisomers of beta-amyloid peptide (1–42)-induced superoxide production in microglia and degeneration of cortical and mesencephalic neurons. J Pharmacol Exp Ther. 302:1212–1219. 2002. View Article : Google Scholar : PubMed/NCBI


Chang RC, Rota C, Glover RE, Mason RP and Hong JS: A novel effect of an opioid receptor antagonist, naloxone, on the production of reactive oxygen species by microglia: a study by electron paramagnetic resonance spectroscopy. Brain Res. 854:224–229. 2000. View Article : Google Scholar : PubMed/NCBI


Liu B, Du L, Kong LY, et al: Reduction by naloxone of lipopolysaccharide-induced neurotoxicity in mouse cortical neuron-glia co-cultures. Neuroscience. 97:749–756. 2000. View Article : Google Scholar : PubMed/NCBI


Liu Y, Qin L, Li G, et al: Dextromethorphan protects dopaminergic neurons against inflammation-mediated degeneration through inhibition of microglial activation. J Pharmacol Exp Ther. 305:212–218. 2003. View Article : Google Scholar : PubMed/NCBI


Li G, Liu Y, Tzeng NS, et al: Protective effect of dextromethorphan against endotoxic shock in mice. Biochem Pharmacol. 69:233–240. 2005. View Article : Google Scholar : PubMed/NCBI


Hansen JJ, Bross P, Westergaard M, et al: Genomic structure of the human mitochondrial chaperonin genes: HSP60 and HSP10 are localised head to head on chromosome 2 separated by a bidirectional promoter. Hum Genet. 112:71–77. 2003. View Article : Google Scholar


Lin L, Kim SC, Wang Y, Gupta S, et al: HSP60 in heart failure: abnormal distribution and role in cardiac myocyte apoptosis. Am J Physiol Heart Circ Physiol. 293:H2238–H2247. 2007. View Article : Google Scholar : PubMed/NCBI


Kreutzberg GW: Microglia: a sensor for pathological events in the CNS. Trends Neurosci. 19:312–318. 1996. View Article : Google Scholar : PubMed/NCBI


Park E, Kim DY and Chun HS: Resveratrol inhibits lipopolysaccharide-induced phagocytotic activity in BV2 cells. J Korean Soc Appl Biol Chem. 55:803–807. 2012. View Article : Google Scholar


Karlstetter M, Lippe E, Walczak Y, et al: Curcumin is a potent modulator of microglial gene expression and migration. J Neuroinflammation. 8:1252011. View Article : Google Scholar : PubMed/NCBI


Park HY, Han MH, Park C, et al: Anti-inflammatory effects of fucoidan through inhibition of NF-κB, MAPK and Akt activation in lipopolysaccharide-induced BV2 microglia cells. Food Chem Toxicol. 49:1745–1752. 2011. View Article : Google Scholar : PubMed/NCBI


Britton P, Lu XC, Laskosky MS and Tortella FC: Dextromethorphan protects against cerebral injury following transient, but not permanent, focal ischemia in rats. Life Sci. 60:1729–1740. 1997. View Article : Google Scholar : PubMed/NCBI


Lesage AS, De Loore KL, Peeters L and Leysen JE: Neuroprotective sigma ligands interfere with the glutamate-activated NOS pathway in hippocampal cell culture. Synapse. 20:156–164. 1995. View Article : Google Scholar : PubMed/NCBI


Prince DA and Feeser HR: Dextromethorphan protects against cerebral infarction in a rat model of hypoxia-ischemia. Neurosci Lett. 85:291–296. 1988. View Article : Google Scholar : PubMed/NCBI


Berman FW and Murray TF: Characterization of [3H]MK-801 binding to N-methyl-D-aspartate receptors in cultured rat cerebellar granule neurons and involvement in glutamate-mediated toxicity. J Biochem Toxicol. 11:217–226. 1996. View Article : Google Scholar


Craviso GL and Musacchio JM: High-affinity dextromethorphan binding sites in guinea pig brain. I Initial characterization. Mol Pharmacol. 23:619–628. 1983a.


Craviso GL and Musacchio JM: High-affinity dextromethorphan binding sites in guinea pig brain. II Competition experiments. Mol Pharmacol. 23:629–640. 1983b.


Khasnavis S, Jana A, Roy A, et al: Suppression of nuclear factor-κB activation and inflammation in microglia by physically modified saline. J Biol Chem. 287:29529–29542. 2012. View Article : Google Scholar : PubMed/NCBI


Gu JH, Ge JB, Li M, et al: Inhibition of NF-κB activation is associated with anti-inflammatory and anti-apoptotic effects of Ginkgolide B in a mouse model of cerebral ischemia/reperfusion injury. Eur J Pharm Sci. 47:652–660. 2012. View Article : Google Scholar : PubMed/NCBI


Woods DC, White YA, Dau C and Johnson AL: TLR4 activates NF-κB in human ovarian granulosa tumor cells. Biochem Biophys Res Commun. 409:675–680. 2011. View Article : Google Scholar : PubMed/NCBI


Soria JA, Arroyo DS, Gaviglio EA, et al: Interleukin 4 induces the apoptosis of mouse microglial cells by a caspase-dependent mechanism. Neurobiol Dis. 43:616–624. 2011. View Article : Google Scholar : PubMed/NCBI


Burguillos MA, Deierborg T, Kavanagh E, et al: Caspase signalling controls microglia activation and neurotoxicity. Nature. 472:319–324. 2011. View Article : Google Scholar : PubMed/NCBI


Kim SC, Stice JP, Chen L, et al: Extracellular heat shock protein 60, cardiac myocytes and apoptosis. Circ Res. 105:1186–1195. 2009. View Article : Google Scholar : PubMed/NCBI


Wang Y, Chen L, Hagiwara N and Knowlton AA: Regulation of heat shock protein 60 and 72 expression in the failing heart. J Mol Cell Cardiol. 48:360–366. 2010. View Article : Google Scholar :


Kröncke KD, Fehsel K and Kolb-Bachofen V: Inducible nitric oxide synthase and its product nitric oxide, a small molecule with complex biological activities. Biol Chem Hoppe Seyler. 376:327–343. 1995.PubMed/NCBI

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Cheng W, Li Y, Hou X, Bai B, Li F, Ding F, Ma J, Zhang N, Shen Y, Wang Y, Wang Y, et al: Determining the neuroprotective effects of dextromethorphan in lipopolysaccharide‑stimulated BV2 microglia. Mol Med Rep 11: 1132-1138, 2015
Cheng, W., Li, Y., Hou, X., Bai, B., Li, F., Ding, F. ... Wang, Y. (2015). Determining the neuroprotective effects of dextromethorphan in lipopolysaccharide‑stimulated BV2 microglia. Molecular Medicine Reports, 11, 1132-1138.
Cheng, W., Li, Y., Hou, X., Bai, B., Li, F., Ding, F., Ma, J., Zhang, N., Shen, Y., Wang, Y."Determining the neuroprotective effects of dextromethorphan in lipopolysaccharide‑stimulated BV2 microglia". Molecular Medicine Reports 11.2 (2015): 1132-1138.
Cheng, W., Li, Y., Hou, X., Bai, B., Li, F., Ding, F., Ma, J., Zhang, N., Shen, Y., Wang, Y."Determining the neuroprotective effects of dextromethorphan in lipopolysaccharide‑stimulated BV2 microglia". Molecular Medicine Reports 11, no. 2 (2015): 1132-1138.