TY  - JOUR
AU  - Schreiber, Stefanie
AU  - Bernal Moya, Jose
AU  - Arndt, Philipp
AU  - Schreiber, Frank
AU  - Müller, Patrick
AU  - Morton, Lorena
AU  - Braun-Dullaeus, Rüdiger Christian
AU  - Valdés-Hernández, Maria Del Carmen
AU  - Duarte, Roberto
AU  - Wardlaw, Joanna Marguerite
AU  - Meuth, Sven Günther
AU  - Mietzner, Grazia
AU  - Vielhaber, Stefan
AU  - Dunay, Ildiko Rita
AU  - Dityatev, Alexander
AU  - Jandke, Solveig
AU  - Mattern, Hendrik
TI  - Brain Vascular Health in ALS Is Mediated through Motor Cortex Microvascular Integrity.
JO  - Cells
VL  - 12
IS  - 6
SN  - 2073-4409
CY  - Basel
PB  - MDPI
M1  - DZNE-2023-00399
SP  - 957
PY  - 2023
N1  - CC BY
AB  - 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.
KW  - Humans
KW  - Amyotrophic Lateral Sclerosis: metabolism
KW  - Motor Cortex: metabolism
KW  - Vascular Endothelial Growth Factor A: metabolism
KW  - Motor Neurons: pathology
KW  - Blood-Brain Barrier: pathology
KW  - amyotrophic lateral sclerosis (Other)
KW  - exerkines (Other)
KW  - motor cortex (Other)
KW  - pericytes (Other)
KW  - vascular supply (Other)
KW  - Vascular Endothelial Growth Factor A (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:36980297
C2  - pmc:PMC10047140
DO  - DOI:10.3390/cells12060957
UR  - https://pub.dzne.de/record/257330
ER  -