4 research outputs found
A longitudinal pilot study on cognition and cerebral hemodynamics in a mouse model of preeclampsia superimposed on hypertension : looking at mothers and their offspring
Preeclampsia is a common hypertensive disorder in pregnant women and whose
causes and consequences have focused primarily on cardiovascular outcomes on the
mother and offspring, often without taking into consideration the possible effects on
the brain. One possible cause of preeclampsia has been attributed to alterations in
the renin-angiotensin system, which has also been linked to cognitive decline. In this
pilot study, we use a transgenic mouse model that chronically overexpresses human
angiotensinogen and renin (R+A
+ mice) that displayed characteristics of preeclampsia
such as proteinuria during gestation. Offspring of these mothers as well as from
control mothers were also examined. We were primarily interested in detecting whether
cognitive deficits were present in the mothers and offspring in the long term and used
a spatial learning and memory task as well as an object recognition task at three
timepoints: 3, 8, and 12 months post-partum or post-natal, while measuring blood
pressure and performing urine analysis after each timepoint. While we did not find
significant deficits in preeclamptic mothers at the later timepoints, we did observe
negative consequences in the pups of R+A
+ mice that coincided with hemodynamic
alterations whereby pups had higher whisker-evoked oxygenated hemoglobin levels and
increased cerebral blood flow responses compared to control pups. Our study provides
validation of this preeclampsia mouse model for future studies to decipher the underlying
mechanisms of long-term cognitive deficits found in offspring
A functional cerebral endothelium is necessary to protect against cognitive decline
A vascular insult occurring early in disease onset may initiate cognitive decline leading to dementia, while pharmacological and lifestyle interventions can prevent this progression. Mice with a selective, tamoxifen-inducible deletion of NF-κB essential modulator (Nemo) in brain endothelial cells were studied as a model of vascular cognitive impairment. Groups included Nemo(Fl) controls and three Nemo(beKO) groups: One untreated, and two treated with simvastatin or exercise. Social preference and nesting were impaired in Nemo(beKO) mice and were not countered by treatments. Cerebrovascular function was compromised in Nemo(beKO) groups regardless of treatment, with decreased changes in sensory-evoked cerebral blood flow and total hemoglobin levels, and impaired endothelium-dependent vasodilation. Nemo(beKO) mice had increased string vessel pathology, blood-brain barrier disruption, neuroinflammation, and reduced cortical somatostatin-containing interneurons. These alterations were reversed when endothelial function was recovered. Findings strongly suggest that damage to the cerebral endothelium can trigger pathologies associated with dementia and its functional integrity should be an effective target in future therapeutic efforts