Journal
ACTA NEUROPATHOLOGICA COMMUNICATIONS
Volume 4, Issue -, Pages -Publisher
BMC
DOI: 10.1186/s40478-016-0350-3
Keywords
Astrocytes; vascular cognitive impairment; Glia; NF-kB; Diffusion tensor imaging (DTI); Neuroinflammation
Categories
Funding
- Network Of Centres Of Excellence In Neurodegeneration (CoEN)
- EU Joint Programme-Neurodegenerative Disease Research (JPND) program (EU Horizon 2020 research and innovation program) [643417/DACAPO-AD]
- DZNE
Ask authors/readers for more resources
Vascular cognitive impairment is the second most common form of dementia. The pathogenic pathways leading to vascular cognitive impairment remain unclear but clinical and experimental data have shown that chronic reactive astrogliosis occurs within white matter lesions, indicating that a sustained pro-inflammatory environment affecting the white matter may contribute towards disease progression. To model vascular cognitive impairment, we induced prolonged mild cerebral hypoperfusion in mice by bilateral common carotid artery stenosis. This chronic hypoperfusion resulted in reactive gliosis of astrocytes and microglia within white matter tracts, demyelination and axonal degeneration, consecutive spatial memory deficits, and loss of white matter integrity, as measured by ultra high-field magnetic resonance diffusion tensor imaging. White matter astrogliosis was accompanied by activation of the pro-inflammatory transcription factor nuclear factor (NF)-kB in reactive astrocytes. Using mice expressing a dominant negative inhibitor of NF-kB under the control of the astrocyte-specific glial fibrillary acid protein (GFAP) promoter (GFAP-IkB alpha-dn), we found that transgenic inhibition of astroglial NF-kB signaling ameliorated gliosis and axonal loss, maintained white matter structural integrity, and preserved memory function. Collectively, our results imply that pro-inflammatory changes in white matter astrocytes may represent an important detrimental component in the pathogenesis of vascular cognitive impairment, and that targeting these pathways may lead to novel therapeutic strategies.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available