Vascular oxidative stress causes neutrophil arrest in brain capillaries, leading to decreased cerebral blood flow and contributing to memory impairment in a mouse model of Alzheimerâ™s disease.
bioRxiv
; 2023 Feb 15.
Article
em En
| MEDLINE
| ID: mdl-36824768
ABSTRACT
INTRODUCTION:
In this study, we explore the role of oxidative stress produced by NOX2-containing NADPH oxidase as a molecular mechanism causing capillary stalling and cerebral blood flow deficits in the APP/PS1 mouse model of AD.METHODS:
We inhibited NOX2 in APP/PS1 mice by administering a 10 mg/kg dose of the peptide inhibitor gp91-ds-tat i.p., for two weeks. We used in vivo two-photon imaging to measure capillary stalling, penetrating arteriole flow, and vascular inflammation. We also characterized short-term memory function and gene expression changes in cerebral microvessels.RESULTS:
We found that after NOX2 inhibition capillary stalling, as well as parenchymal and vascular inflammation, were significantly reduced. In addition, we found a significant increase in penetrating arteriole flow, followed by an improvement in short-term memory, and downregulation of inflammatory gene expression pathways.DISCUSSION:
Oxidative stress is a major mechanism leading to microvascular dysfunction in AD, and represents an important therapeutic target.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Tipo de estudo:
Etiology_studies
Idioma:
En
Revista:
BioRxiv
Ano de publicação:
2023
Tipo de documento:
Article