Pericyte remodeling is deficient in the aged brain and contributes to impaired capillary flow and structure

Berthiaume, Andrée-Anne; Schmid, Franca; Stamenković, Stefan; Coelho‐Santos, Vanessa; Nielson, Cara D.; Weber, Bruno; Majesky, Mark W.; Shih, Andy Y.

doi:10.1038/s41467-022-33464-w

Cited by 60 publications

(45 citation statements)

References 74 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Increased development of pericyte-targeted therapies is predicted within the next 10 years. Targeting pericyte dysfunction has the potential to restore microvascular integrity, tone, perfusion and clearance [ 69 , 151 ]. Pharmaceutical interventions targeting brain pericytes have already been approved.…”

Section: Targeting Brain Vascular Health To Preserve Microvascular In...mentioning

confidence: 99%

Brain Vascular Health in ALS Is Mediated through Motor Cortex Microvascular Integrity

Schreiber

Bernal

Ulbrich

et al. 2023

Cells

View full text Add to dashboard Cite

Brain vascular health appears to be critical for preventing the development of amyotrophic lateral sclerosis (ALS) and slowing its progression. ALS patients often demonstrate cardiovascular risk factors and commonly suffer from cerebrovascular disease, with evidence of pathological alterations in their small cerebral blood vessels. Impaired vascular brain health has detrimental effects on motor neurons: vascular endothelial growth factor levels are lowered in ALS, which can compromise endothelial cell formation and the integrity of the blood–brain barrier. Increased turnover of neurovascular unit cells precedes their senescence, which, together with pericyte alterations, further fosters the failure of toxic metabolite removal. We here provide a comprehensive overview of the pathogenesis of impaired brain vascular health in ALS and how novel magnetic resonance imaging techniques can aid its detection. In particular, we discuss vascular patterns of blood supply to the motor cortex with the number of branches from the anterior and middle cerebral arteries acting as a novel marker of resistance and resilience against downstream effects of vascular risk and events in ALS. We outline how certain interventions adapted to patient needs and capabilities have the potential to mechanistically target the brain microvasculature towards favorable motor cortex blood supply patterns. Through this strategy, we aim to guide novel approaches to ALS management and a better understanding of ALS pathophysiology.

show abstract

Section: Targeting Brain Vascular Health To Preserve Microvascular In...mentioning

confidence: 99%

Brain Vascular Health in ALS Is Mediated through Motor Cortex Microvascular Integrity

Schreiber

Bernal

Ulbrich

et al. 2023

Cells

View full text Add to dashboard Cite

show abstract

“…Increased development of pericyte-targeted therapies has been predicted within the next 10 years. Targeting pericyte dysfunction has the potential to restore microvascular integrity, tone, perfusion, and clearance [69,151]. Pharmaceutical interventions targeting brain pericytes have already been approved.…”

Section: Pericyte Restorationmentioning

confidence: 99%

Brain Vascular Health in ALS Is Mediated through Motor Cortex Microvascular Integrity

Schreiber¹,

Bernal²,

Ulbrich³

et al. 2023

Preprint

View full text Add to dashboard Cite

Brain vascular health appears to be of critical importance for protection against the development of amyotrophic lateral sclerosis (ALS) as well as the slowing of disease progression. ALS patients often demonstrate cardiovascular risk factors and commonly suffer from cerebrovascular disease, with evidence of pathological alterations in the small cerebral vessels. Impaired vascular brain health has detrimental effects on motor neurons as lowered vascular endothelial growth factor levels compromise endothelial cell formation, promoting blood-brain barrier leakage and inflammation. Increased turnover of neurovascular unit cells precedes their senescence, which, together with pericyte alterations, further fosters the failure of toxic metabolite removal. We here provide a comprehensive overview of the pathogenesis of impaired brain vascular health in ALS and how novel magnetic resonance imaging techniques can aid its detection. In particular, we discuss vascular patterns of blood supply to the motor cortex with the number of branches from the anterior and middle cerebral arteries acting as a novel marker of resistance and resilience against downstream effects of vascular risk and events in ALS. We outline how certain interventions adapted to patient needs and capabilities have the potential to mechanistically target the brain microvasculature towards favorable motor cortex blood supply patterns. Through this strategy, we aim to guide novel approaches to ALS management and a better understanding of ALS pathophysiology.

show abstract

“…They suggest that pericyte loss is sufficient to cause abnormal redistribution of blood flow in capillary networks, stalling of blood cells, and vascular regression. 126,127 No information is available on the effect of pericyte loss on capillary perfusion in the cerebral white matter and the hippocampus. Furthermore, questions remain on what causes pericyte loss in AD/ADRD.…”

Section: Prospective Studies and Opportunitiesmentioning

confidence: 99%

Deep Imaging to Dissect Microvascular Contributions to White Matter Degeneration in Rodent Models of Dementia

Stamenković¹,

Li²,

Waters

et al. 2023

Stroke

Self Cite

View full text Add to dashboard Cite

The increasing socio-economic burden of Alzheimer disease (AD) and AD-related dementias has created a pressing need to define targets for therapeutic intervention. Deficits in cerebral blood flow and neurovascular function have emerged as early contributors to disease progression. However, the cause, progression, and consequence of small vessel disease in AD/AD-related dementias remains poorly understood, making therapeutic targets difficult to pinpoint. Animal models that recapitulate features of AD/AD-related dementias may provide mechanistic insight because microvascular pathology can be studied as it develops in vivo. Recent advances in in vivo optical and ultrasound-based imaging of the rodent brain facilitate this goal by providing access to deeper brain structures, including white matter and hippocampus, which are more vulnerable to injury during cerebrovascular disease. Here, we highlight these novel imaging approaches and discuss their potential for improving our understanding of vascular contributions to AD/AD-related dementias.

show abstract

Pericyte remodeling is deficient in the aged brain and contributes to impaired capillary flow and structure

Cited by 60 publications

References 74 publications

Brain Vascular Health in ALS Is Mediated through Motor Cortex Microvascular Integrity

Brain Vascular Health in ALS Is Mediated through Motor Cortex Microvascular Integrity

Brain Vascular Health in ALS Is Mediated through Motor Cortex Microvascular Integrity

Deep Imaging to Dissect Microvascular Contributions to White Matter Degeneration in Rodent Models of Dementia

Contact Info

Product

Resources

About