We study the role that neuroimmune mechanisms play in brain function under physiological conditions and during neurological disease. Our main cells of interest are microglia, the resident immune cells of the central nervous system. Microglia are the first responders to any pathological insult—whether injury or disease— but their role in the physiological brain was greatly underappreciated for decades. Moreover, microglia have also historically been synonymous with inflammatory processes that can further damage neurons in the context of disease.
Using advanced microscopy technologies to follow the behavior of individual cells inside the intact living brain in real time, we previously showed—for the first time—that microglia continuously survey their environment and can rapidly contain small injuries within a few minutes without causing inflammatory damage. These findings inspired numerous studies aimed at understanding the mechanisms and the significance of such unexpectedly dynamic microglial functions for neuronal development, plasticity, function, and dysfunction.
Our recent studies have focused on microglial responses in the context of blood-brain barrier disruption, a pathological phenomenon that is very common among neurological diseases such as multiple sclerosis, Alzheimer’s disease, and stroke. We have also developed and published novel methods for imaging the living brain and spinal cord to follow ongoing biological processes over time. Our research combines cutting-edge imaging techniques with molecular, cellular and genetic approaches to study the interactions between blood vessels, neurons, and glia, and to better understand how their structural and functional relationships change between health and disease. By studying these relationships in real time, our ultimate goal is to expand our understanding of the role of microglia in brain function, and to identify new targets for therapeutic intervention for neurological diseases.
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2. Tsai HH, Niu J, Munji R, Davalos D, Chang J, Zhang H, Tien AC, Kuo CJ, Chan JR, Daneman R, Fancy SP. (2016) Oligodendrocyte precursors migrate along vasculature in the developing nervous system. Science 351(6271):379-84. PMID: 26798014
3. Akassoglou K, Agalliu D, Chang CJ, Davalos D, Grutzendler J, Hillman EM, Khakh BS, Kleinfeld D, McGavern DB, Nelson SJ, Zlokovic BV. (2016) Neurovascular and Immuno-Imaging: From Mechanisms to Therapies. Proceedings of the Inaugural Symposium. Front Neurosci 10:46. PMID: 26941593; PMCID: PMC4761864
4. Baeza-Raja B, Sachs BD, Li P, Christian F, Vagena E, Davalos D, Le Moan N, Ryu JK, Sikorski SL, Chan JP, Scadeng M, Taylor SS, Houslay MD, Baillie GS, Saltiel AR, Olefsky JM, Akassoglou K. (2016) p75 Neurotrophin Receptor Regulates Energy Balance in Obesity. Cell Rep 14(2):255-68. PMID: 26748707; PMCID: PMC4831919
5. Le Moan N, Baeten KM, Rafalski VA, Ryu JK, Rios Coronado PE, Bedard C, Syme C, Davalos D, Akassoglou K. (2015) Hypoxia Inducible Factor-1α in Astrocytes and/or Myeloid Cells Is Not Required for the Development of Autoimmune Demyelinating Disease. eNeuro 2(2). PMID: 26213713; PMCID: PMC4511492
6. Gyoneva S, Davalos D, Biswas D, Swanger SA, Garnier-Amblard E, Loth F, Akassoglou K, Traynelis SF. (2014) Systemic inflammation regulates microglial responses to tissue damage in vivo. Glia 62(8):1345-60. PMID: 24807189; PMCID: PMC4408916
7. Davalos D, Baeten KM, Whitney MA, Mullins ES, Friedman B, Olson ES, Ryu JK, Smirnoff DS, Petersen MA, Bedard C, Degen JL, Tsien RY, Akassoglou K. (2014) Early detection of thrombin activity in neuroinflammatory disease. Ann Neurol 75(2):303-8. PMID: 24740641; PMCID: PMC4049631
8. Chen W, Guo Y, Walker EJ, Shen F, Jun K, Oh SP, Degos V, Lawton MT, Tihan T, Davalos D, Akassoglou K, Nelson J, Pile-Spellman J, Su H, Young WL. (2013) Reduced mural cell coverage and impaired vessel integrity after angiogenic stimulation in the Alk1-deficient brain. Arterioscler Thromb Vasc Biol 33(2):305-10. PMID: 23241407; PMCID: PMC3569037
9. Merlini M, Davalos D, Akassoglou K. (2012) In vivo imaging of the neurovascular unit in CNS disease. Intravital 1(2):87-94. PMID: 25197615; PMCID: PMC4155511
10. Davalos D, Ryu JK, Merlini M, Baeten KM, Le Moan N, Petersen MA, Deerinck TJ, Smirnoff DS, Bedard C, Hakozaki H, Gonias Murray S, Ling JB, Lassmann H, Degen JL, Ellisman MH, Akassoglou K. (2012) Fibrinogen-induced perivascular microglial clustering is required for the development of axonal damage in neuroinflammation. Nat Commun 3:1227. PMID: 23187627; PMCID: PMC3514498
11. Kwan W, Träger U, Davalos D, Chou A, Bouchard J, Andre R, Miller A, Weiss A, Giorgini F, Cheah C, Möller T, Stella N, Akassoglou K, Tabrizi SJ, Muchowski PJ. (2012) Mutant huntingtin impairs immune cell migration in Huntington disease. J Clin Invest 122(12):4737-47. PMID: 23160193; PMCID: PMC3533551
12. Baeza-Raja B, Li P, Le Moan N, Sachs BD, Schachtrup C, Davalos D, Vagena E, Bridges D, Kim C, Saltiel AR, Olefsky JM, Akassoglou K. (2012) p75 neurotrophin receptor regulates glucose homeostasis and insulin sensitivity. Proc Natl Acad Sci U S A 109(15):5838-43. PMID: 22460790; PMCID: PMC3326459
13. Davalos D, Akassoglou K. (2012) In vivo imaging of the mouse spinal cord using two-photon microscopy. J Vis Exp Jan 5;(59):e2760. PMID: 22258623; PMCID: PMC3369767
14. Davalos D, Akassoglou K. (2012) Fibrinogen as a key regulator of inflammation in disease. Semin Immunopathol 34(1):43-62. PMID: 22037947
15. Drew PJ, Shih AY, Driscoll JD, Knutsen PM, Blinder P, Davalos D, Akassoglou K, Tsai PS, Kleinfeld D. (2010) Chronic optical access through a polished and reinforced thinned skull. Nat Methods 7(12):981-4. PMID: 20966916; PMCID: PMC3204312
16. Ryu JK, Davalos D, Akassoglou K. (2009) Fibrinogen signal transduction in the nervous system. J Thromb Haemost 7 Suppl 1:151-4. PMID: 19630789; PMCID: PMC2888044
17. Davalos D, Lee JK, Smith WB, Brinkman B, Ellisman MH, Zheng B, Akassoglou K. (2008) Stable in vivo imaging of densely populated glia, axons and blood vessels in the mouse spinal cord using two-photon microscopy. J Neurosci Methods 169(1):1-7. PMID: 18192022; PMCID: PMC2647134
18. Adams RA, Schachtrup C, Davalos D, Tsigelny I, Akassoglou K. (2007) Fibrinogen signal transduction as a mediator and therapeutic target in inflammation: lessons from multiple sclerosis. Curr Med Chem 14(27):2925-36. PMID: 18045138
19. Davalos D, Grutzendler J, Yang G, Kim JV, Zuo Y, Jung S, Littman DR, Dustin ML, Gan WB. (2005) ATP mediates rapid microglial response to local brain injury in vivo. Nat Neurosci 8(6):752-8. PMID: 15895084