Strong Impact of Chronic Cerebral Hypoperfusion on Neurovascular Unit,Cerebrovascular Remodeling,and Neurovascular Trophic Coupling in Alzheimer’s Disease Model Mouse
Restricted accessResearch articleFirst published online April 26, 2016
Strong Impact of Chronic Cerebral Hypoperfusion on Neurovascular Unit,Cerebrovascular Remodeling,and Neurovascular Trophic Coupling in Alzheimer’s Disease Model Mouse
Although chronic cerebral hypoperfusion (CCH) may affect Alzheimer’s disease (AD)
pathogenesis, the mechanism remains elusive. In the present study, we investigated the
role of CCH on an AD mouse model in neurovascular unit, cerebrovascular remodeling, and
neurovascular trophic coupling. Moreover, examined protective effect of galantamine.
Alzheimer’s disease transgenic mice (APP23) were subjected to bilateral common carotid
arteries stenosis with ameroid constrictors for slowly progressive cerebral hypoperfusion.
CCH exacerbated neuronal loss and decrease of α7 subunit of nicotinic
acetylcholine receptors (α7-nAChRs) expression in hippocampus and
thalamus at 12 months. Meanwhile, CCH greatly induced advanced glycation end products
expression, and blood-brain barrier leakage through observing IgG and MMP9 expressions.
Furthermore, a significant number of dramatic enlarged cerebral vessels with remodeling,
BDNF/TrkB decreased in neurovascular trophic coupling. The present study demonstrated that
CCH strongly enhanced primary AD pathology including neurodegeneration, neurovascular unit
disruption, cerebrovascular remodeling and neurovascular trophic coupling damage in AD
mice, and that galantamine treatment greatly ameliorated such neuropathologic
abnormalities.
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