ji.zhang [at] mcgill.ca (Email)
Tel:(514) 398-7203 ext. 00036
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The main stream of our research program is to investigate the immune etiology of chronic pain by exploring the interactions between injured neurons and their surrounding glia/immune cells and the impact of glial activation in pain behaviour. Chronic pain is a sensory disorder resulting from infection, injury, cancer or some metabolic/neurodegenerative diseases, which has an enormous negative impact on the quality of life of individuals affected by this problem. While for decades, a neuron-centric view has predominated to explain the pathophysiology of chronic pain, recent work has uncovered extensive neuroimmune interactions as substrates. Interactions between the immune and nervous systems occur at multiple levels, where different types of glia/immune cells and immune-derived substances are implicated at different stages of the pathogenesis. We have identified that chemokine MCP-1, released by damaged neurons is a trigger in inducing spinal microglial activation which is necessary for the development of hypersensitivity (J Neurochem, J of Neuroscience). Our results also demonstrated that spinal microglial activation induced by peripheral nerve injury is not just a property of those cells that already existed in the spinal cord, there include populations of cells coming from proliferation and recruitment of blood-born macrophages (J of Neuroscience, Pain). By using well established animal models of chronic pain, molecular, neuroanatomical and behaviroal approaches, we are currently focusing on:
- Characterizing the glial phenotypes in the circumstance of inflammation, nerve injury and chronic neurodegenerative diseases, and the correlation with pain behaviour
- Examining the impact of neuron-glia, neuron-immune interaction in the pathogenesis of chronic pain
- Developing new therapeutic strategy by targeting both spinal glial cells and bone marrow derived macrophages for an effective pain relief.
In addition to our activities in pain research, we are also interested in exploring the impact of normal aging on glial cell biology. We want to understand aging dependent glial degeneration and the impacts of glial senescence on neuronal functions.
Articles in peer reviewed journals.
SeungHwan Lee and Ji Zhang (2012) Heterogeneity of macrophages in injured trigeminal nerves: Cytokine/chemokine expressing vs. phagocytic macrophages Brain, Behavior and Immunity 2012 Mar 25. [Epub ahead of print]
SSV Padi, Xiang Q Shi, Yuan Q Zhao, Michael R. Ruff, Noel Baichoo, Candace B. Pert, and Ji Zhang (2012) Attenuation of Rodent Neuropathic Pain by an Orally Active Peptide, RAP-103, which Potently Blocks CCR2 and CCR5 Mediated Monocyte Chemotaxis and Inflammation Pain 153(1):95-106
S Nadeau, M Filali, J Zhang, Bradley Kerr, S Rivest, D Soulet, Y Iwakura, JP de Rivero Vaccari, RW. Keane, and S Lacroix (2011) Functional Recovery after Peripheral Nerve Injury is Dependent on the Pro-Inflammatory Cytokines IL-1b; and TNF-a: Implications for Neuropathic Pain J of Neuroscience 31(35):12533-12542
S Echeverry, XQ Shi, S Rivest , J Zhang (2011) Peripheral nerve injury alters blood spinal cord barrier functional and molecular integrity through a selective inflammatory pathway J of Neuroscience 31(30):10819-28
XQ Shi, T Lim, YQ Zhao, J Zhang (2011) Statins alleviate experimental nerve injury induced neuropathic pain Pain 152(5):1033-43
SH Lee, YQ Zhao, A Ribeiro-da-Silva, J Zhang (2010) Distinctive response of CNS glial cells in oro-facial pain associated with injury, infection and inflammation Molecular Pain 6:79
XQ Shi, H Zekki and J Zhang (2010) Role of TLR2 in nerve injury induced-neuropathic pain is essentially mediated through peripheral inflammatory response Glia 59: 231-241
S Echeverry, XQ Shi, A Haw, L Hong, ZW Zhang, J Zhang (2009). Transforming growth factor beta1 impairs neuropathic pain through pleiotropic effect. Molecular Pain 27, 5: 16
S Echeverry, XQ Shi, J Zhang (2008). Characterization of cell proliferation in rat spinal cord following peripheral nerve injury. Pain 135 (1-2): 37-47
J Zhang, XQ Shi, S Echeverry, JS Mogil, Y De Koninck, S Rivest (2007) Expression of CCR2 in both resident and bone marrow-derived microglia plays a critical role in neuropathic pain. J of Neuroscience 27(45): 12396-12406
J. Zhang, Y. De Koninck (2006). Spatial and temporal relationship between MCP-1 expression and spinal microglial activation following peripheral nerve injury. J.Neurochem. 97, 772-783
F Mennicken, J Zhang, C Hoffert, S Ahmad, A Beaudet, D O'Donnell (2003). Phylogenetic changes in the expression of delta opioid receptors in spinal cord and dorsal root ganglia. J. Comp. Neurol. 465(3): 349-60.
J Zhang, C Hoffert, HK Vu, T Groblewski, S Ahmad, D O'Donnell (2003). Induction of CB2 receptor expression in the rat spinal cord of neuropathic but not inflammatory chronic pain models. Eur. J. Neurosci, 17(12): 2750-4.
PMC Lembo, E Grazzini, T Groblewski, D O'Donnell, M-O Roy, J Zhang, C Hoffert, J Cao, R Schmidt, M Pelletier, M Labarre, M Gosselin, Y Fortin, D Banville, SH Shen, P Ström, K Payza, A Dray, P Walker & S Ahmad (2002). Proenkephalin A gene products activate a new family of sensory neuron-specific GPCRs. Nature Neuroscience, Vol 5, No 3: 201-209
V Blais, J Zhang, S Rivest (2002). In altering the release of glucocorticoids, ketorolac exacerbates the effects of systemic immune stimuli on expression of proinflammatory genes in the brain. Endocrinology, 143(12): 4820-7.
J Zhang and S Rivest (2001). Anti-inflammatory effects of prostaglandin E2 in the central nervous system in response to brain injury and circulating lipopolysaccharide. J.Neurochem. 2001 Feb; 76(3): 855-64.
J Zhang and S Rivest. (2000). A functional analysis of EP4 receptor-expressing neurons in mediating the action of prostaglandin E2 within specific nuclei of the brain in response to circulating interleukin-1beta. J. Neurochem. 74 (5): 2134-45
J Zhang and S Rivest (1999). Distribution, regulation and colocalization of the genes encoding the EP2- and EP4-PGE2 receptors in the rat brain and neuronal responses to systemic inflammation. Eur. J. Neurosci. 11 (8): 2651-68.
D Djordjijevic, J Zhang, M Priam, C Villoet, D Gourdji, C Kordon and J Epelbaum (1998). Effect of 17beta-estradiol on somatostatin receptor expression and inhibitory effects on growth hormone and prolactin release in rat pituitary cell cultures. Endocrinology 139 (5): 2272-7
C Viollet, C Lanneau, A Faivre-Bauman, J Zhang, D Djorjijevic, C Loudres, R Gardette, C Kordon, J Epelbaum (1997). Distinct patterns of expression and physiological effects of sst1 and sst2 receptor subtypes in mouse hypothalamic neurons and astrocytes in culture. J. Neurochem. 68 (6): 2273-80.
C Viollet, A Faivre-Bauman, J Zhang, C Llorens-Cortes, C Loudres, C Kordon, J Epelbaum (1995). Differential expression of somatostatin receptors by quantitative PCR in the rat brain. C. R. Acad. Sci. III. 318(8): 851-7.
Reviews, book chapters, books
S Echeverry, SH Lee, T Lim, J Zhang (2011) Inflammation mediates nerve injury triggered neuropathic pain In Nerve injury, InTech Open Access Publisher (in press).
J Zhang and Y De Koninck (2009) Abnormal central neuroimmune interactions. In Functional Chronic Pain Syndromes: Similarities and Differences in Clinical Presentation and Pathophysiology, IASP Press. Chapter 15, 319-336.
RJ. Miller, W Rostene, E Apartis, G Banisadr, K Biber, ED. Milligan, FA. White, J Zhang (2008). Chemokine action in the nervous system. J of Neuroscience 28(46):11792-5
J Zhang and S Echeverry (2007) Monocyte chemoattractant protein-1 and chronic pain. In Leah R. Grinwald (ed) Chemokine research trends, Novapublishers. Chapter 7, p107-120.
J Zhang (2006). Involvement of monocyte chemoattractant protein-1 in peripheral nerve injury induced neuropathic pain. Reviews in Analgesia 9: 13-20.
J Zhang and S Rivest (2004) Arachidonate metabolites in neurophysiological system: The fever pathway. In The Eicosanoids JohnWiley& Sons Limited. Chapter 42, 463-472.
J Zhang and S Rivest (2003). Is survival possible without arachidonate metabolites in the brain during systemic infection? News in Physiological Sciences, 18:137-142.
S Rivest, S Lacroix, L Valliere, S Nadeau, J Zhang and N Laflamme (2000). How the blood talks to the brain parenchyma and the paraventricular nucleus of the hypothalamus during systemic inflammatory and infectious stimuli. Proc. Soc. Exp. Biol. Med. 223 (1): 22-38.
J Epelbaum, N Briard, D Djordjijevic, A Dutour, W Meyerhoff, C Olivier, A Slama, C Viollet, J Zhang (1998). Characterization of somatostatin receptor subtypes in mammalian pituitary. N Y Acad Sci. 15; 839: 249-53