Honors & Awards

  • Young Investigator Award, 13th International Symposium on Healthy Aging (03/2018)
  • Best Oral Presentation, The 8th Symposium for Cross-straits, Hong Kong and Macao on Free Radical Biology and Medicine (09/24/2018)
  • Travel Award, 2018 World life Science (10/29/2018)
  • Ph.D. studentship, University of Hong Kong (2011-2015)

Professional Education

  • B.Sc., Sun Yat-Sen University, Biochemistry (2011)
  • PhD, University of New Mexico, Exchange student (2014)
  • Ph.D., The University of Hong Kong, Medicine (2016)

Stanford Advisors

Community and International Work

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    MDPI journals



    Ongoing Project


    Opportunities for Student Involvement


  • Volunteer

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    Ongoing Project


    Opportunities for Student Involvement


  • Reviewer

    Partnering Organization(s)


    Ongoing Project


    Opportunities for Student Involvement


  • Reviewer

    Partnering Organization(s)

    Journal of Toxicology and Applied Pharmacology

    Ongoing Project


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Research & Scholarship

Current Research and Scholarly Interests

Immune and Nervous Systems Interaction; Ischemic Postconditioning; Optogenetics


All Publications

  • Targeting Myeloperoxidase (MPO) Mediated Oxidative Stress and Inflammation for Reducing Brain Ischemia Injury: Potential Application of Natural Compounds FRONTIERS IN PHYSIOLOGY Chen, S., Chen, H., Du, Q., Shen, J. 2020; 11: 433


    Oxidative stress and inflammation are two critical pathological processes of cerebral ischemia-reperfusion injury. Myeloperoxidase (MPO) is a critical inflammatory enzyme and therapeutic target triggering both oxidative stress and neuroinflammation in the pathological process of cerebral ischemia-reperfusion injury. MPO is presented in infiltrated neutrophils, activated microglial cells, neurons, and astrocytes in the ischemic brain. Activation of MPO can catalyze the reaction of chloride and H2O2 to produce HOCl. MPO also mediates oxidative stress by promoting the production of reactive oxygen species (ROS) and reactive nitrogen species (RNS), modulating the polarization and inflammation-related signaling pathways in microglia and neutrophils. MPO can be a therapeutic target for attenuating oxidative damage and neuroinflammation in ischemic stroke. Targeting MPO with inhibitors or gene deficiency significantly reduced brain infarction and improved neurological outcomes. This article discusses the important roles of MPO in mediating oxidative stress and neuroinflammation during cerebral ischemia-reperfusion injury and reviews the current understanding of the underlying mechanisms. Furthermore, we summarize the active compounds from medicinal herbs with potential as MPO inhibitors for anti-oxidative stress and anti-inflammation to attenuate cerebral ischemia-reperfusion injury, and as adjunct therapeutic agents for extending the window of thrombolytic treatment. We highlight that targeting MPO could be a promising strategy for alleviating ischemic brain injury, which merits further translational study.

    View details for DOI 10.3389/fphys.2020.00433

    View details for Web of Science ID 000538441200001

    View details for PubMedID 32508671

    View details for PubMedCentralID PMC7248223

  • Potential Natural Compounds for Preventing 2019-nCoV Infection Chen, H., Du, Q. 2020
  • A Highly Selective and Sensitive Chemiluminescent Probe for Real-Time Monitoring of Hydrogen Peroxide in Cells and Animals. Angewandte Chemie (International ed. in English) Yang, D., Ye, S., Hananya, N., Green, O., Chen, H., Zhao, A. Q., Shen, J., Shabat, D. 2020


    Selective and sensitive molecular probes for hydrogen peroxide (H 2 O 2 ), which plays diverse roles in oxidative stress and redox signalling, are urgently needed to investigate the physiological and pathological effects of H 2 O 2 . A lack of reliable tools for in vivo imaging has hampered the development of H 2 O 2 mediated therapeutics. By combining a specific tandem Payne/Dakin reaction with a chemiluminescent scaffold, H 2 O 2 -CL-510 was developed as a highly selective and sensitive probe for detection of H 2 O 2 both in vitro and in vivo . A rapid 430-fold enhancement of chemiluminescence was triggered directly by H 2 O 2 without any laser excitation. Arsenic trioxide induced oxidative damage in leukemia was successfully detected. In particular, cerebral ischemia-reperfusion injury induced H 2 O 2 fluxes were visualized in rat brains using H 2 O 2 -CL-510 , providing a new chemical tool for real-time monitoring of H 2 O 2 dynamics in living animals.

    View details for DOI 10.1002/anie.202005429

    View details for PubMedID 32472602

  • Therapeutic Targets of Oxidative/Nitrosative Stress and Neuroinflammation in Ischemic Stroke: Applications for Natural Product Efficacy with Omics and Systemic Biology. Pharmacological research Chen, H., He, Y., Chen, S., Qi, S., Shen, J. 2020: 104877


    Oxidative/nitrosative stress and neuroinflammation are critical pathological processes in cerebral ischemia-reperfusion injury, and their intimate interactions mediate neuronal damage, blood-brain barrier (BBB) damage and hemorrhagic transformation (HT) during ischemic stroke. We review current progress towards understanding the interactions of oxidative/nitrosative stress and inflammatory responses in ischemic brain injury. The interactions between reactive oxygen species (ROS)/reactive nitrogen species (RNS) and innate immune receptors such as TLR2/4, NOD-like receptor, RAGE, and scavenger receptors are crucial pathological mechanisms that amplify brain damage during cerebral ischemic brain injury. Furthermore, we review the current progress of omics and systematic biology approaches for studying complex network regulations related to oxidative/nitrosative stress and inflammation in the pathology of ischemic stroke. Targeting oxidative/nitrosative stress and neuroinflammation could be a promising therapeutic strategy for ischemic stroke treatment. We then review recent advances in discovering compounds from medicinal herbs with the bioactivities of simultaneously regulating oxidative/nitrosative stress and pro-inflammatory molecules for minimizing ischemic brain injury. These compounds include sesamin, baicalin, salvianolic acid A, 6-paradol, silymarin, apocynin, 3H-1,2-Dithiole-3-thione, (-)-epicatechin, rutin, Dl-3-N-butylphthalide, and naringin. We finally summarize recent developments of the omics and systematic biology approaches for exploring the molecular mechanisms and active compounds of Traditional Chinese Medicine (TCM) formulae with the properties of antioxidant and anti-inflammation for neuroprotection. The comprehensive omics and systematic biology approaches provide powerful tools for exploring therapeutic principles of TCM formulae and developing precision medicine for stroke treatment.

    View details for DOI 10.1016/j.phrs.2020.104877

    View details for PubMedID 32407958

  • Astragaloside VI Promotes Neural Stem Cell Proliferation and Enhances Neurological Function Recovery in Transient Cerebral Ischemic Injuryvia Activating EGFR/MAPK Signaling Cascades MOLECULAR NEUROBIOLOGY Chen, X., Wu, H., Chen, H., Wang, Q., Xie, X., Shen, J. 2019; 56 (4): 3053?67


    Radix Astragali (AR) is a commonly used medicinal herb for post-stroke disability in Traditional Chinese Medicine but its active compounds for promoting neurogenic effects are largely unknown. In the present study, we tested the hypothesis that Astragaloside VI could be a promising active compound from AR for adult neurogenesis and brain repair via targeting epidermal growth factor (EGF)-mediated MAPK signaling pathway in post-stroke treatment. By using cultured neural stem cells (NSCs) and experimental stroke rat model, we investigated the effects of Astragaloside VI on inducing NSCs proliferation and self-renewal in vitro, and enhancing neurogenesis for the recovery of the neurological functions in post-ischemic brains in vivo. For animal experiments, rats were undergone 1.5 h middle cerebral artery occlusion (MCAO) plus 7 days reperfusion. Astragaloside VI (2 ?g/kg) was daily administrated by intravenous injection (i.v.) for 7 days. Astragaloside VI treatment promoted neurogenesis and astrogenic formation in dentate gyrus zone, subventricular zone, and cortex of the transient ischemic rat brains in vivo. Astragaloside VI treatment enhanced NSCs self-renewal and proliferation in the cultured NSCs in vitro without affecting NSCs differentiation. Western blot analysis showed that Astragaloside VI up-regulated the expression of nestin, p-EGFR and p-MAPK, and increased neurosphere sizes, whose effects were abolished by the co-treatment of EGF receptor inhibitor gefitinib and ERK inhibitor PD98059. Behavior tests revealed that Astragaloside VI promoted the spatial learning and memory and improved the impaired motor function in transient cerebral ischemic rats. Taken together, Astragaloside VI could effectively activate EGFR/MAPK signaling cascades, promote NSCs proliferation and neurogenesis in transient cerebral ischemic brains, and improve the repair of neurological functions in post-ischemic stroke rats. Astragaloside VI could be a new therapeutic drug candidate for post-stroke treatment.

    View details for DOI 10.1007/s12035-018-1294-3

    View details for Web of Science ID 000465498200059

    View details for PubMedID 30088176

  • Kinesin-1 Regulates Extrasynaptic Targeting of NMDARs and Neuronal Vulnerability Toward Excitotoxicity ISCIENCE Lin, R., Duan, Z., Sun, H., Fung, M., Chen, H., Wang, J., Lau, C., Yang, D., Liu, Y., Ni, Y., Wang, Z., Cui, J., Wu, W., Yung, W., Chan, Y., Lo, A. Y., Xia, J., Shen, J., Huang, J. 2019; 13: 82-+


    N-methyl-D-aspartate (NMDA) receptor (NMDAR) is highly compartmentalized in neurons, and its dysfunction has been implicated in various neuropsychiatric and neurodegenerative disorders. Recent failure to exploit NMDAR antagonization as a potential therapeutic target has driven the need to identify molecular mechanisms that regulate NMDAR compartmentalization. Here, we report that the reduction of Kif5b, the heavy chain of kinesin-1, protected neurons against NMDA-induced excitotoxicity and ischemia-provoked neurodegeneration. Direct binding of kinesin-1 to the GluN2B cytoplasmic tails regulated the levels of NMDAR at extrasynaptic sites and the subsequent influx of calcium mediated by extrasynaptic NMDAR by regulating the insertion of NMDARs into neuronal surface. Transient increase of Kif5b restored the surface levels of NMDAR and the decreased neuronal susceptibility to NMDA-induced excitotoxicity. The expression of Kif5b was repressed in cerebral ischemia preconditioning. Our findings reveal that kinesin-1 regulates extrasynaptic NMDAR targeting and signaling, and the reduction of kinesin-1 could be exploited to defer neurodegeneration.

    View details for DOI 10.1016/j.isci.2019.02.009

    View details for Web of Science ID 000462829500008

    View details for PubMedID 30826728

    View details for PubMedCentralID PMC6402234

  • Glycyrrhizin Prevents Hemorrhagic Transformation and Improves Neurological Outcome in Ischemic Stroke with Delayed Thrombolysis Through Targeting Peroxynitrite-Mediated HMGB1 Signaling. Translational stroke research Chen, H., Guan, B., Wang, B., Pu, H., Bai, X., Chen, X., Liu, J., Li, C., Qiu, J., Yang, D., Liu, K., Wang, Q., Qi, S., Shen, J. 2019


    Peroxynitrite (ONOO-) and high mobility group box 1 protein (HMGB1) are important cytotoxic factors contributing to cerebral ischemia-reperfusion injury. However, the roles of ONOO- in mediating HMGB1 expression and its impacts on hemorrhagic transformation (HT) in ischemic brain injury with delayed t-PA treatment remain unclear. In the present study, we tested the hypothesis that ONOO- could directly mediate the activation and release of HMGB1 in ischemic brains with delayed t-PA treatment. With clinical studies, we found that plasma nitrotyrosine (NT, a surrogate marker of ONOO-) was positively correlated with HMGB1 level in acute ischemic stroke patients. Hemorrhagic transformation and t-PA-treated ischemic stroke patients had increased levels of nitrotyrosine and HMGB1 in plasma. In animal experiments, we found that FeTmPyP, a representative ONOO- decomposition catalyst (PDC), significantly reduced the expression of HMGB1 and its receptor TLR2, and inhibited MMP-9 activation, preserved collagen IV and tight junction claudin-5 in ischemic rat brains with delayed t-PA treatment. ONOO- donor SIN-1 directly induced expression of HMGB1 and its receptor TLR2 in naive rat brains in vivo and induced HMGB1 in brain microvascular endothelial b.End3 cells in vitro. Those results suggest that ONOO- could activate HMGB1/TLR2/MMP-9 signaling. We then addressed whether glycyrrhizin, a natural HMGB1 inhibitor, could inhibit ONOO- production and the antioxidant properties of glycyrrhizin contribute to the inhibition of HMGB1 and the neuroprotective effects on attenuating hemorrhagic transformation in ischemic stroke with delayed t-PA treatment. Glycyrrhizin treatment downregulated the expressions of NADPH oxidase p47 phox and p67 phox and iNOS, inhibited superoxide and ONOO- production, reduced the expression of HMGB1, TLR2, MMP-9, preserved type IV collagen and claudin-5 in ischemic brains. Furthermore, glycyrrhizin significantly decreased the mortality rate, attenuated hemorrhagic transformation, brain swelling, blood-brain barrier damage, neuronal apoptosis, and improved neurological outcomes in the ischemic stroke rat model with delayed t-PA treatment. In conclusion, peroxynitrite-mediated HMGB1/TLR2 signaling contributes to hemorrhagic transformation, and glycyrrhizin could be a potential adjuvant therapy to attenuate hemorrhagic transformation, possibly through inhibiting the ONOO-/HMGB1/TLR2 signaling cascades.

    View details for DOI 10.1007/s12975-019-00772-1

    View details for PubMedID 31872339

  • Active compounds and molecular targets of Chinese herbal medicine for neurogenesis in stroke treatment: Implication for cross talk between Traditional Chinese Medicine and Biomedical Sciences World Journal of Traditional Chinese Medicine Chen, X., Chen, H., Shen, J. 2019
  • Potential molecular targets of peroxynitrite in mediating blood-brain barrier damage and haemorrhagic transformation in acute ischaemic stroke with delayed tissue plasminogen activator treatment FREE RADICAL RESEARCH Chen, H., Chen, X., Luo, Y., Shen, J. 2018; 52 (11-12): 1220?39


    Tissue plasminogen activator (t-PA) remains to be the only FDA-approved drug for ischaemic stroke, but it has a restrictive therapeutic window with 4.5?hours. Beyond the golden time window, thrombolytic treatment carries the risk of haemorrhagic transformation (HT). The blood-brain barrier (BBB) disruption is a critical step in the t-PA-mediated HT. Although large efforts are made to explore the mechanisms of the BBB disruption and HT, the underlying mechanisms are largely unknown. Thrombolytic treatment for recanalization could produce reactive oxygen species (ROS) and reactive nitrogen species (RNS) and mediate cerebral ischaemia-reperfusion injury. RNS, including nitric oxide (NO) and peroxynitrite (ONOO-), are important players in cerebral ischaemia-reperfusion injury. In particular, ONOO- and its derivatives could mediate neurovascular unit damages and induce the BBB disruption and HT possibly through interacting with different cellular signalling pathways including matrix metalloproteinase (MMPs), high mobility group Box 1 (HMGB1), toll-like receptor2/4, poly(ADP-ribose) polymerase, Src, ROCK, and GSK-3?. Herein, we review current progress about the roles of ONOO- in mediating those signalling pathways and their impacts on the t-PA-induced BBB disruption and HT. Subsequently, we discuss the values of natural compounds with the properties of scavenging ONOO- as adjunctive therapies to extend the therapeutic window of t-PA and attenuate haemorrhage transformation in ischaemic stroke.

    View details for DOI 10.1080/10715762.2018.1521519

    View details for Web of Science ID 000457432500004

    View details for PubMedID 30468092

  • Baicalin Attenuates Blood-Brain Barrier Disruption and Hemorrhagic Transformation and Improves Neurological Outcome in Ischemic Stroke Rats with Delayed t-PA Treatment: Involvement of ONOO--MMP-9 Pathway TRANSLATIONAL STROKE RESEARCH Chen, H., Guan, B., Chen, X., Chen, X., Li, C., Qiu, J., Yang, D., Liu, K., Qi, S., Shen, J. 2018; 9 (5): 515?29


    Tissue plasminogen activator (t-PA) has a restrictive therapeutic window within 4.5 h after ischemic stroke with the risk of hemorrhagic transformation (HT) and neurotoxicity when it is used beyond the time window. In the present study, we tested the hypothesis that baicalin, an active compound of medicinal plant, could attenuate HT in cerebral ischemia stroke with delayed t-PA treatment. Male Sprague-Dawley rats were subjected to middle cerebral artery occlusion (MCAO) for 4.5 h and then continuously received t-PA infusion (10 mg/kg) for 0.5 h and followed by 19-h reperfusion. Baicalin (50, 100, 150 mg/kg) was administrated via femoral vein at 4.5 h after MCAO cerebral ischemia. Delayed t-PA infusion significantly increased the mortality rate, induced HT, blood-brain barrier (BBB) damage, and apoptotic cell death in the ischemic brains and exacerbated neurological outcomes in cerebral ischemia-reperfusion rats at 24 h after MCAO cerebral ischemia. Co-treatment of baicalin significantly reduced the mortality rates, ameliorated the t-PA-mediated BBB disruption and HT. Furthermore, baicalin showed to directly scavenge peroxynitrite and inhibit MMP-9 expression and activity in the ischemic brains with the delayed t-PA treatment. Baicalin had no effect on the t-PA fibrinolytic function indicated by t-PA activity assay. Taken together, baicalin could attenuate t-PA-mediated HT and improve the outcomes of ischemic stroke treatment possibly via inhibiting peroxynitrite-mediated MMP-9 activation.

    View details for DOI 10.1007/s12975-017-0598-3

    View details for Web of Science ID 000444426000009

    View details for PubMedID 29275501

  • Targeting RNS/caveolin-1/MMP signaling cascades to protect against cerebral ischemia-reperfusion injuries: potential application for drug discovery ACTA PHARMACOLOGICA SINICA Chen, H., Chen, X., Li, W., Shen, J. 2018; 39 (5): 669?82


    Reactive nitrogen species (RNS) play important roles in mediating cerebral ischemia-reperfusion injury. RNS activate multiple signaling pathways and participate in different cellular events in cerebral ischemia-reperfusion injury. Recent studies have indicated that caveolin-1 and matrix metalloproteinase (MMP) are important signaling molecules in the pathological process of ischemic brain injury. During cerebral ischemia-reperfusion, the production of nitric oxide (NO) and peroxynitrite (ONOO-), two representative RNS, down-regulates the expression of caveolin-1 (Cav-1) and, in turn, further activates nitric oxide synthase (NOS) to promote RNS generation. The increased RNS further induce MMP activation and mediate disruption of the blood-brain barrier (BBB), aggravating the brain damage in cerebral ischemia-reperfusion injury. Therefore, the feedback interaction among RNS/Cav-1/MMPs provides an amplified mechanism for aggravating ischemic brain damage during cerebral ischemia-reperfusion injury. Targeting the RNS/Cav-1/MMP pathway could be a promising therapeutic strategy for protecting against cerebral ischemia-reperfusion injury. In this mini-review article, we highlight the important role of the RNS/Cav-1/MMP signaling cascades in ischemic stroke injury and review the current progress of studies seeking therapeutic compounds targeting the RNS/Cav-1/MMP signaling cascades to attenuate cerebral ischemia-reperfusion injury. Several representative natural compounds, including calycosin-7-O-?-D-glucoside, baicalin, Momordica charantia polysaccharide (MCP), chlorogenic acid, lutein and lycopene, have shown potential for targeting the RNS/Cav-1/MMP signaling pathway to protect the brain in ischemic stroke. Therefore, the RNS/Cav-1/MMP pathway is an important therapeutic target in ischemic stroke treatment.

    View details for DOI 10.1038/aps.2018.27

    View details for Web of Science ID 000431513300003

    View details for PubMedID 29595191

    View details for PubMedCentralID PMC5943912

  • Peroxynitrite enhances self-renewal, proliferation and neuronal differentiation of neural stem/progenitor cells through activating HIF-1 alpha and Wnt/beta-catenin signaling pathway FREE RADICAL BIOLOGY AND MEDICINE Chen, X., Zhou, B., Yan, T., Wu, H., Feng, J., Chen, H., Gao, C., Peng, T., Yang, D., Shen, J. 2018; 117: 158?67


    Hypoxic/ischemic stimulation could mediate growth and differentiation of neural stem/progenitor cells (NSCs) into mature neurons but its underlying mechanisms are largely unclear. Peroxynitrite formation is considered as a crucial pathological process contributing to cerebral ischemia-reperfusion injury. In the present study, we tested the hypothesis that peroxynitrite at low concentration could function as redox signaling to promote the growth of NSCs under hypoxic/ischemic conditions. Increased NSCs proliferation was accompanied by peroxynitrite production in the rat brains with 1?h of ischemia plus 7 days of reperfusion in vivo. Cell sorting experiments revealed that endogenous peroxynitrite level affected the capacity of proliferation and self-renewal in NSCs in vitro. Hypoxia stimulated peroxynitrite production and promoted NSCs self-renewal, proliferation and neuronal differentiation whereas treatments of peroxynitrite decomposition catalysts (PDCs, FeTMPyP and FeTPPS) blocked the changes in NSCs self-renewal, proliferation and neuronal differentiation. Exogenous peroxynitrite treatment revealed similar effects to promote NSCs proliferation, self-renewal and neuronal differentiation. Furthermore, the neurogenesis-promoting effects of peroxynitrite were partly through activating HIF-1? correlated with enhanced Wnt/?-catenin signaling pathway. In conclusion, peroxynitrite could be a cellular redox signaling for promoting NSCs proliferation, self-renewal and neuronal differentiation and peroxynitrite production could contribute to neurogenesis in ischemic/hypoxic NSCs.

    View details for DOI 10.1016/j.freeradbiomed.2018.02.011

    View details for Web of Science ID 000427420600016

    View details for PubMedID 29427793

  • One-Compound-Multi-Target: Combination Prospect of Natural Compounds with Thrombolytic Therapy in Acute Ischemic Stroke CURRENT NEUROPHARMACOLOGY Chen, H., Qi, S., Shen, J. 2017; 15 (1): 134?56


    Tissue plasminogen activator (t-PA) is the only FDA-approved drug for acute ischemic stroke treatment, but its clinical use is limited due to the narrow therapeutic time window and severe adverse effects, including hemorrhagic transformation (HT) and neurotoxicity. One of the potential resolutions is to use adjunct therapies to reduce the side effects and extend t-PA's therapeutic time window. However, therapies modulating single target seem not to be satisfied, and a multitarget strategy is warranted to resolve such complex disease. Recently, large amount of efforts have been made to explore the active compounds from herbal supplements to treat ischemic stroke. Some natural compounds revealed both neuro- and bloodbrain- barrier (BBB)-protective effects by concurrently targeting multiple cellular signaling pathways in cerebral ischemia-reperfusion injury. Thus, those compounds are potential to be one-drug-multi-target agents as combined therapy with t-PA for ischemic stroke. In this review article, we summarize current progress about molecular targets involving in t-PA-mediated HT and neurotoxicity in ischemic brain injury. Based on these targets, we select 23 promising compounds from currently available literature with the bioactivities simultaneously targeting several important molecular targets. We propose that those compounds merit further investigation as combined therapy with t-PA. Finally, we discuss the potential drawbacks of the natural compounds' studies and raise several important issues to be addressed in the future for the development of natural compound as an adjunct therapy.

    View details for DOI 10.2174/1570159X14666160620102055

    View details for Web of Science ID 000391855800015

    View details for PubMedID 27334020

    View details for PubMedCentralID PMC5327453

  • Baicalin Reduces Hemorrhagic Transformation of Rat Ischemic Stroke with Delayed T-PA Treatment Chen, H., Shen, J. ELSEVIER SCIENCE INC. 2016: S159
  • Glycyrrhizin Could Inhibit HMGB1-MMP-9 Signaling and Prevent Hemorrhagic Transformation in Ischemic Stroke with Delayed T-PA Treatment Shen, J., Chen, H. ELSEVIER SCIENCE INC. 2016: S167
  • Caveolin-1 Is Critical for Lymphocyte Trafficking into Central Nervous System during Experimental Autoimmune Encephalomyelitis JOURNAL OF NEUROSCIENCE Wu, H., Deng, R., Chen, X., Wong, W., Chen, H., Gao, L., Nie, Y., Wu, W., Shen, J. 2016; 36 (19): 5193?99


    Multiple sclerosis (MS) is a progressive autoimmune disease of the CNS with its underlying mechanisms not fully understood. In the present study, we tested the hypothesis that caveolin-1, a major membrane scaffolding protein, plays a critical role in the pathogenesis of experimental autoimmune encephalomyelitis, a laboratory murine model of MS. We found increased expression of caveolin-1 in serum and spinal cord tissues in association with disease incidence and severity in wild-type mice with active encephalomyelitis. After immunization, Cav-1 knock-out mice showed remarkable disease resistance with decreased incidence and clinical symptoms. Furthermore, Cav-1 knock-out mice had alleviated encephalitogenic T cells trafficking into the CNS with decreased expressions of adhesion molecules ICAM-1 and VCAM-1 within the lesions. In agreement with in vivo studies, in vitro knockdown of caveolin-1 compromised the upregulation of ICAM-1 in endothelial cells, leading to the amelioration of the transendothelial migration of pathogenic TH1 and TH17 cells. Together, those results indicate that caveolin-1 serves as an active modulator of CNS-directed lymphocyte trafficking and could be a therapeutic target for neuroinflammatory diseases, such as multiple sclerosis.The hallmark feature of neuroinflammatory diseases is the massive infiltrations of encephalitogenic leukocytes into the CNS parenchyma, a process that remains largely unclear. Our study demonstrates the critical contribution of caveolin-1 to encephalomyelitis pathogenesis and CNS-directed lymphocyte trafficking by modulation of adhesion molecules ICAM-1 and VCAM-1, highlighting the pathological involvement of caveolin-1 in neuroinflammatory diseases.

    View details for DOI 10.1523/JNEUROSCI.3734-15.2016

    View details for Web of Science ID 000378279500003

    View details for PubMedID 27170118

    View details for PubMedCentralID PMC6601805

  • Targeting ONOO-/HMGB1/MMP-9 Signaling Cascades: Potential for Drug Development from Chinese Medicine to Attenuate Ischemic Brain Injury and Hemorrhagic Transformation Induced by Thrombolytic Treatment Integrative Medicine International Chen, H., Guan, B., Shen, J. 2016

    View details for DOI 10.1159/000442468

  • Peroxynitrite Decomposition Catalyst Reduces Delayed Thrombolysis-induced Hemorrhagic Transformation in Ischemia-reperfused Rat Brains CNS NEUROSCIENCE & THERAPEUTICS Chen, H., Chen, X., Feng, J., Liu, K., Qi, S., Shen, J. 2015; 21 (7): 585?90


    Hemorrhagic transformation (HT) is a major complication of delayed tissue plasminogen activator (t-PA) treatment in ischemic stroke. We aimed to explore whether peroxynitrite decomposition catalyst (PDC) could prevent such complication.Male Sprague-Dawley (SD) rats were subjected to middle cerebral artery occlusion (MCAO) with t-PA (10 mg/kg) or t-PA plus FeTMPyP (3 mg/kg, a representative PDC) at MCAO for 2 or 5 h and reperfusion for 22 or 19 h, respectively. HT was assessed with hemoglobin assay. Neurological deficit was evaluated with Modified Neurological Severity Score (mNSS). Peroxynitrite formation was examined by detecting 3-nitrotyrosine (3-NT) formation. The expression and activity of MMP-9/MMP-2 were assessed by Western blotting and gelatin zymography.t-PA treatment at 2 h of MCAO did not induce HT but attenuated neurological deficit, whereas treatment at 5 h significantly induced HT and worsened the neurological outcome. Such complications were prevented by FeTMPyP cotreatment. Early t-PA treatment inhibited 3-NT and MMP-9/MMP-2 expression, whereas delayed treatment induced 3-NT and MMP-9/MMP-2 expression and activity. FeTMPyP cotreatment downregulated 3-NT and inhibited MMP-9/MMP-2 in both time points.Peroxynitrite decomposition catalyst could prevent hemorrhagic transformation and improve neurological outcome ischemic rat brains with delayed t-PA treatment via inhibiting peroxynitrite-mediated MMP activation.

    View details for DOI 10.1111/cns.12406

    View details for Web of Science ID 000356704000007

    View details for PubMedID 25996167

    View details for PubMedCentralID PMC6495263

  • Momordica charantia polysaccharides could protect against cerebral ischemia/reperfusion injury through inhibiting oxidative stress mediated c-Jun N-terminal kinase 3 signaling pathway NEUROPHARMACOLOGY Gong, J., Sun, F., Li, Y., Zhou, X., Duan, Z., Duan, F., Zhao, L., Chen, H., Qi, S., Shen, J. 2015; 91: 123?34


    Momordica charantia (MC) is a medicinal plant for stroke treatment in Traditional Chinese Medicine, but its active compounds and molecular targets are unknown yet. M. charantia polysaccharide (MCP) is one of the important bioactive components in MC. In the present study, we tested the hypothesis that MCP has neuroprotective effects against cerebral ischemia/reperfusion injury through scavenging superoxide (O2(-)), nitric oxide (NO) and peroxynitrite (ONOO(-)) and inhibiting c-Jun N-terminal protein kinase (JNK3) signaling cascades. We conducted experiments with in vivo global and focal cerebral ischemia/reperfusion rat models and in vitro oxygen glucose deprivation (OGD) neural cells. The effects of MCP on apoptotic cell death and infarction volume, the bioactivities of scavenging O2(-), NO and ONOO(-), inhibiting lipid peroxidation and modulating JNK3 signaling pathway were investigated. Major results are summarized as below: (1) MCP dose-dependently attenuated apoptotic cell death in neural cells under OGD condition in vitro and reduced infarction volume in ischemic brains in vivo; (2) MCP had directing scavenging effects on NO, O2(-) and ONOO(-) and inhibited lipid peroxidation; (3) MCP inhibited the activations of JNK3/c-Jun/Fas-L and JNK3/cytochrome C/caspases-3 signaling cascades in ischemic brains in vivo. Taken together, we conclude that MCP could be a promising neuroprotective ingredient of M. charantia and its mechanisms could be at least in part attributed to its antioxidant activities and inhibiting JNK3 signaling cascades during cerebral ischemia/reperfusion injury.

    View details for DOI 10.1016/j.neuropharm.2014.11.020

    View details for Web of Science ID 000350926100015

    View details for PubMedID 25510970

  • Pros and cons of current approaches for detecting peroxynitrite and their applications Biomedical Journal Chen, X., Chen, H., Deng, R., Shen, J. 2014; 37

    View details for DOI 10.4103/2319-4170.134084

  • Targeting reactive nitrogen species: a promising therapeutic strategy for cerebral ischemia-reperfusion injury ACTA PHARMACOLOGICA SINICA Chen, X., Chen, H., Xu, M., Shen, J. 2013; 34 (1): 67?77


    Ischemic stroke accounts for nearly 80% of stroke cases. Recanalization with thrombolysis is a currently crucial therapeutic strategy for re-building blood supply, but the thrombolytic therapy often companies with cerebral ischemia-reperfusion injury, which are mediated by free radicals. As an important component of free radicals, reactive nitrogen species (RNS), including nitric oxide (NO) and peroxynitrite (ONOO(-)), play important roles in the process of cerebral ischemia-reperfusion injury. Ischemia-reperfusion results in the production of nitric oxide (NO) and peroxynitrite (ONOO(-)) in ischemic brain, which trigger numerous molecular cascades and lead to disruption of the blood brain barrier and exacerbate brain damage. There are few therapeutic strategies available for saving ischemic brains and preventing the subsequent brain damage. Recent evidence suggests that RNS could be a therapeutic target for the treatment of cerebral ischemia-reperfusion injury. Herein, we reviewed the recent progress regarding the roles of RNS in the process of cerebral ischemic-reperfusion injury and discussed the potentials of drug development that target NO and ONOO(-) to treat ischemic stroke. We conclude that modulation for RNS level could be an important therapeutic strategy for preventing cerebral ischemia-reperfusion injury.

    View details for DOI 10.1038/aps.2012.82

    View details for Web of Science ID 000314191000012

    View details for PubMedID 22842734

    View details for PubMedCentralID PMC4086503

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