Safety of oral anticoagulants on experimental brain microbleeding and cognition.
Neuropharmacology
; 155: 162-172, 2019 09 01.
Article
em En
| MEDLINE
| ID: mdl-31132437
ABSTRACT
This study aims at determining the ability of clinical-based doses of four oral anticoagulants to transform the onset of a cerebral microhemorrhages (CMH) burden into a symptomatic intracerebral hemorrhage (ICH) in the healthy brain, and precipitate cognitive impairment. Wild-type mice were anticoagulated for 10 days using apixaban, rivaroxaban or dabigatran as direct oral anticoagulants (DOACs), or warfarin as vitamin K-antagonist. Meanwhile, a burden of â¼20 CMHs was induced in the Sylvian territory by intra-carotid injection of cyclodextrin nanoparticles. At bleeding onset, only warfarin provoked deadly hematoma, and dramatically increased mortality (+45%). All the DOACs enhanced CMH burden through a greater number of intermediate-sized microhemorrhages (+80% to +180%). Although silent at onset, both baseline- and anticoagulant-enhanced CMH burdens increased mortality (+11% to +58%) along the following year without statistical difference among groups, and despite cessation of anticoagulation and absence of CMH progression or transformation into ICH. All survivor mice exhibited reduction in visual recognition memory from 9 months. In the healthy brain, DOACs preserve the onset of microhemorrhages from transformation into ICH, and do not precipitate cognitive impairment despite enhancement of CMH burden. High CMH burdens should however be considered for early detection and preventive memory care apart from anticoagulation decisions.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Hemorragia Cerebral
/
Cognição
/
Microvasos
/
Anticoagulantes
Tipo de estudo:
Prognostic_studies
/
Screening_studies
Limite:
Animals
Idioma:
En
Revista:
Neuropharmacology
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
França