Preprint Review Version 1 Preserved in Portico This version is not peer-reviewed

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

Stefanie Schreiber
* ORCID logo ,
Jose Bernal
,
Philipp Ulbrich
,
Frank Schreiber
,
Patrick Müller
,
Rüdiger Christian Braun-Dullaeus
,
Maria Del Carmen Valdés-Hernándes
ORCID logo ,
Roberto Duarte
,
Joanna Marguerite Wardlaw
ORCID logo ,
Sven Günther Meuth
,
Grazia Mietzner
,
Stefan Vielhaber
,
Alexander Dityatev
ORCID logo ,
Solveig Jandke
ORCID logo ,
Hendrik Mattern
Version 1 : Received: 10 February 2023 / Approved: 17 February 2023 / Online: 17 February 2023 (04:47:49 CET)

A peer-reviewed article of this Preprint also exists.

Schreiber, S.; Bernal, J.; Arndt, P.; Schreiber, F.; Müller, P.; Morton, L.; Braun-Dullaeus, R.C.; Valdés-Hernández, M.D.C.; Duarte, R.; Wardlaw, J.M.; Meuth, S.G.; Mietzner, G.; Vielhaber, S.; Dunay, I.R.; Dityatev, A.; Jandke, S.; Mattern, H. Brain Vascular Health in ALS Is Mediated through Motor Cortex Microvascular Integrity. Cells 2023, 12, 957. Schreiber, S.; Bernal, J.; Arndt, P.; Schreiber, F.; Müller, P.; Morton, L.; Braun-Dullaeus, R.C.; Valdés-Hernández, M.D.C.; Duarte, R.; Wardlaw, J.M.; Meuth, S.G.; Mietzner, G.; Vielhaber, S.; Dunay, I.R.; Dityatev, A.; Jandke, S.; Mattern, H. Brain Vascular Health in ALS Is Mediated through Motor Cortex Microvascular Integrity. Cells 2023, 12, 957.

Abstract

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.

Keywords

amyotrophic lateral sclerosis; vascular supply; motor cortex; pericytes; exerkines

Subject

Medicine and Pharmacology, Neuroscience and Neurology

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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