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
Agner, Shannon C; Klein, Robyn S (2018) Viruses have multiple paths to central nervous system pathology. Curr Opin Neurol 31:313-317
Adusumilli, Gautam; Trinkaus, Kathryn; Sun, Peng et al. (2018) Intensity ratio to improve black hole assessment in multiple sclerosis. Mult Scler Relat Disord 19:140-147
Spees, William M; Lin, Tsen-Hsuan; Sun, Peng et al. (2018) MRI-based assessment of function and dysfunction in myelinated axons. Proc Natl Acad Sci U S A 115:E10225-E10234
Zhan, Jie; Lin, Tsen-Hsuan; Libbey, Jane E et al. (2018) Diffusion Basis Spectrum and Diffusion Tensor Imaging Detect Hippocampal Inflammation and Dendritic Injury in a Virus-Induced Mouse Model of Epilepsy. Front Neurosci 12:77
Klein, Robyn S; Garber, Charise; Howard, Nicole (2017) Infectious immunity in the central nervous system and brain function. Nat Immunol 18:132-141
Lin, Tsen-Hsuan; Chiang, Chia-Wen; Perez-Torres, Carlos J et al. (2017) Diffusion MRI quantifies early axonal loss in the presence of nerve swelling. J Neuroinflammation 14:78
Cross, Anne H; Song, Sheng-Kwei (2017) ""A new imaging modality to non-invasively assess multiple sclerosis pathology"". J Neuroimmunol 304:81-85
Klein, Robyn S; Hunter, Christopher A (2017) Protective and Pathological Immunity during Central Nervous System Infections. Immunity 46:891-909
Hou, Jianghui; Baker, Lane A; Zhou, Lushan et al. (2016) Viral interactions with the blood-brain barrier: old dog, new tricks. Tissue Barriers 4:e1142492
Salimi, Hamid; Cain, Matthew D; Klein, Robyn S (2016) Encephalitic Arboviruses: Emergence, Clinical Presentation, and Neuropathogenesis. Neurotherapeutics 13:514-34

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