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 51 publications

(45 citation statements)

References 74 publications

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“…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

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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.

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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

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“…Pericytes are essential for vasculature's physiological stability, as exemplified by the prominent pericyte-endothelial interactions forming the blood-brain barrier (16). Reduction in pericytes abundance, pericyte detachment from capillaries, and accrual of senescence markers are associated with microvascular fragility and dysfunction, as observed in aging, ischemic disease, fibrotic and neurodegenerative disorders, diabetes, tumors, and COVID-19 (17)(18)(19)(20)(21). Moreover, capillary pericytes modulate blood flow in different organs.…”

Section: Functional Roles Of Pericytesmentioning

confidence: 99%

Approaches for the isolation and long-term expansion of pericytes from human and animal tissues

Alvino

Mohammed

et al. 2023

Front. Cardiovasc. Med.

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Pericytes surround capillaries in every organ of the human body. They are also present around the vasa vasorum, the small blood vessels that supply the walls of larger arteries and veins. The clinical interest in pericytes is rapidly growing, with the recognition of their crucial roles in controlling vascular function and possible therapeutic applications in regenerative medicine. Nonetheless, discrepancies in methods used to define, isolate, and expand pericytes are common and may affect reproducibility. Separating pure pericyte preparations from the continuum of perivascular mesenchymal cells is challenging. Moreover, variations in functional behavior and antigenic phenotype in response to environmental stimuli make it difficult to formulate an unequivocal definition of bona fide pericytes. Very few attempts were made to develop pericytes as a clinical-grade product. Therefore, this review is devoted to appraising current methodologies’ pros and cons and proposing standardization and harmonization improvements. We highlight the importance of developing upgraded protocols to create therapeutic pericyte products according to the regulatory guidelines for clinical manufacturing. Finally, we describe how integrating RNA-seq techniques with single-cell spatial analysis, and functional assays may help realize the full potential of pericytes in health, disease, and tissue repair.

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“…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

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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

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

Cited by 51 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

Approaches for the isolation and long-term expansion of pericytes from human and animal tissues

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

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