Diabetic rats are more susceptible to cognitive decline in a model of
microemboli-mediated vascular contributions to cognitive impairment and
Authors Chandran R, Li W, Ahmed HA, Dong G, Ward RA, He L, Doueiry C, Ergul A
Submitted By Weiguo Li on 11/9/2020
Status Published
Journal Brain research
Year 2020
Date Published
Volume : Pages 1749 : 147132
PubMed Reference 33002484
Abstract Vascular disease plays an important role in all kinds of cognitive impairment
and dementia. Diabetes increases the risk of vascular disease and dementia.
However, it is not clear how existing vascular disease in the brain accelerates
the development of small vessel disease and promotes cognitive dysfunction in
diabetes. We used microemboli (ME) injection model in the current study to test
the hypothesis that cerebrovascular dysfunction in diabetes facilitates
entrapment of ME leading to inflammation and cognitive decline. We investigated
cognitive function, axonal/white matter (WM) changes, neurovascular coupling,
and microglial activation in control and diabetic male and female Wistar rats
subjected to sham or low/high dose ME injection. Diabetic male animals had
cognitive deficits, WM demyelination and greater microglial activation than the
control animals even at baseline. Functional hyperemia gradually declined in
diabetic male animals after ME injection. Both low and high ME injection
worsened WM damage and increased microglial activation in diabetic male and
female animals. Low ME did not cause cognitive decline in controls, while
promoting learning/memory deficits in diabetic female rats and no further
decline in diabetic male animals. High ME led to cognitive decline in control
male rats and exacerbated the deficits in diabetic cohort. These results suggest
that the existing cerebrovascular dysfunction in diabetes may facilitate
ME-mediated demyelination leading to cognitive decline. It is important to
integrate comorbidities/sex as a biological variable into experimental models
for the development of preventive or therapeutic targets.

Investigators with authorship
Weiguo LiMedical University of South Carolina