A functional cerebral endothelium is necessary to protect against cognitive decline.
Lianne J TrigianiMiled BourourouMaría Lacalle-AuriolesClotilde LecruxAmy HynesShoshana SpringDarren J FernandesJohn G SledFrédéric LesageMarkus SchwaningerEdith HamelPublished in: Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism (2021)
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 NemoFl controls and three NemobeKO groups: One untreated, and two treated with simvastatin or exercise. Social preference and nesting were impaired in NemobeKO mice and were not countered by treatments. Cerebrovascular function was compromised in NemobeKO groups regardless of treatment, with decreased changes in sensory-evoked cerebral blood flow and total hemoglobin levels, and impaired endothelium-dependent vasodilation. NemobeKO 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.
Keyphrases
- cognitive decline
- mild cognitive impairment
- cognitive impairment
- blood brain barrier
- cerebral ischemia
- cerebral blood flow
- nitric oxide
- high fat diet induced
- endothelial cells
- physical activity
- subarachnoid hemorrhage
- oxidative stress
- signaling pathway
- healthcare
- traumatic brain injury
- metabolic syndrome
- cardiovascular disease
- mental health
- brain injury
- type diabetes
- high intensity
- skeletal muscle
- combination therapy
- wild type
- current status
- insulin resistance
- lipopolysaccharide induced
- resting state
- white matter
- multiple sclerosis
- red blood cell
- newly diagnosed
- smoking cessation
- cell proliferation