Project 2: """"""""Neuroprotective mechanisms of CXCL12 during CNS demyelinating diseases"""""""" The molecular mechanisms responsible for leukocyte migration and activation within the CNS parenchyma are unknown, as are the mechanisms that orchestrate recovery and myelin repair during remitting phases of both MS and EAE. Blood-brain barrier (BBB) disruption and demyelination are consequences of white matter inflammatory infiltrates22""""""""25. Utilizing confocal microscopy, Dr. Robyn Klein observed the loss of endothelial cell expression of the chemokine CXCL12, normally displays basolateral localization, during CNS autoimmune disease, suggesting CXCL12 plays a role in regulating the blood-brain barrier (BBB). Dr. Klein's team also observed that spinal cord motorneurons express CXCL12 and white matter oligodendrocyte precursors express its receptor CXCR4, suggesting a role for these molecules in remyelination. Thus, a novel, antiinflammatory role for CXCL12 whereby it functions to localize CXCR4-expressing mononuclear cells to the perivascular space, thus limiting their parenchyma! infiltration and activation is proposed in Project 2. Thus, Project 2 will (1) determine how CXCL12-mediated perivascular localization regulates mononuclear cell trafficking during CNS autoimmunity, (2) determine how perivascular localization regulates mononuclear cell activation during CNS autoimmunity, and (3) evaluate how CXCL12 regulates the remyelination process.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Program Projects (P01)
Project #
5P01NS059560-05
Application #
8380929
Study Section
National Institute of Neurological Disorders and Stroke Initial Review Group (NSD)
Project Start
Project End
2014-07-31
Budget Start
2012-08-01
Budget End
2013-07-31
Support Year
5
Fiscal Year
2012
Total Cost
$233,219
Indirect Cost
$79,786
Name
Washington University
Department
Type
DUNS #
068552207
City
Saint Louis
State
MO
Country
United States
Zip Code
63130
Cross, Anne H; Song, Sheng-Kwei (2016) ""A new imaging modality to non-invasively assess multiple sclerosis pathology"". J Neuroimmunol :
Kim, Joong Hee; Song, Sheng-Kwei; Haldar, Justin P (2016) Signal-to-noise ratio-enhancing joint reconstruction for improved diffusion imaging of mouse spinal cord white matter injury. Magn Reson Med 75:852-8
Salimi, Hamid; Cain, Matthew D; Klein, Robyn S (2016) Encephalitic Arboviruses: Emergence, Clinical Presentation, and Neuropathogenesis. Neurotherapeutics 13:514-34
Yue, Xuyi; Jin, Hongjun; Liu, Hui et al. (2015) A potent and selective C-11 labeled PET tracer for imaging sphingosine-1-phosphate receptor 2 in the CNS demonstrates sexually dimorphic expression. Org Biomol Chem 13:7928-39
Cantoni, Claudia; Bollman, Bryan; Licastro, Danilo et al. (2015) TREM2 regulates microglial cell activation in response to demyelination in vivo. Acta Neuropathol 129:429-47
Wang, Yong; Sun, Peng; Wang, Qing et al. (2015) Differentiation and quantification of inflammation, demyelination and axon injury or loss in multiple sclerosis. Brain 138:1223-38
Daniels, Brian P; Klein, Robyn S (2015) Knocking on Closed Doors: Host Interferons Dynamically Regulate Blood-Brain Barrier Function during Viral Infections of the Central Nervous System. PLoS Pathog 11:e1005096
Tu, Tsang-Wei; Budde, Matthew D; Xie, Mingqiang et al. (2014) Phase-aligned multiple spin-echo averaging: a simple way to improve signal-to-noise ratio of in vivo mouse spinal cord diffusion tensor image. Magn Reson Imaging 32:1335-43
Cruz-Orengo, Lillian; Daniels, Brian P; Dorsey, Denise et al. (2014) Enhanced sphingosine-1-phosphate receptor 2 expression underlies female CNS autoimmunity susceptibility. J Clin Invest 124:2571-84
Lin, Tsen-Hsuan; Chiang, Chia-Wen; Trinkaus, Kathryn et al. (2014) Manganese-enhanced MRI (MEMRI) via topical loading of Mn(2+) significantly impairs mouse visual acuity: a comparison with intravitreal injection. NMR Biomed 27:390-8

Showing the most recent 10 out of 54 publications