Targeting Uric Acid Prevents Brain Injury and Anxiety in a Rat Model of Hemorrhagic Shock.
Shock
; 56(2): 298-307, 2021 08 01.
Article
in En
| MEDLINE
| ID: mdl-33394973
ABSTRACT
ABSTRACT Secondary brain injury following hemorrhagic shock (HS) is a frequent complication in patients, even in the absence of direct brain trauma, leading to behavioral changes and more specifically anxiety and depression. Despite preclinical studies showing inflammation and apoptosis in the brain after HS, none have addressed the impact of circulating mediators. Our group demonstrated an increased uric acid (UA) circulation in rats following HS. Since UA is implicated in endothelial dysfunction and inflammatory response, we hypothesized UA could alter the blood-brain barrier (BBB) and impact the brain. Male Wistar rats were randomly assigned to SHAM, HS (hemorrhagic shock) and HSâ+âU (hemorrhagic shock + 1.5âmg/kg of uricase). The uricase intervention, specifically targeting UA, was administered during fluid resuscitation. It prevented BBB dysfunction (fluorescein sodium salt permeability and expression of intercellular adhesion molecule-1) following HS. As for neuroinflammation, all of the results obtained (MPO activity; Iba1 and GFAP expression) showed a significant increase after HS, also prevented by the uricase. The same pattern was observed after quantification of apoptosis (caspase-3 activity and TUNEL) and neurodegeneration (Fluoro-Jade). Finally, the forced swim, elevated plus maze, and social interaction tests detected anxiety-like behavior after HS, which was blunted in rats treated with the uricase. In conclusion, we have identified UA as a new circulatory inflammatory mediator, responsible for brain alterations and anxious behavior after HS in a murine model. The ability to target UA holds the potential of an adjunctive therapeutic solution to reduce brain dysfunction related to hemorrhagic shock in human.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Anxiety
/
Shock, Hemorrhagic
/
Urate Oxidase
/
Uric Acid
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Brain Injuries
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Inflammation Mediators
Type of study:
Etiology_studies
Limits:
Animals
Language:
En
Journal:
Shock
Journal subject:
ANGIOLOGIA
/
CARDIOLOGIA
Year:
2021
Document type:
Article
Affiliation country:
Canada
Publication country:
EEUU
/
ESTADOS UNIDOS
/
ESTADOS UNIDOS DA AMERICA
/
EUA
/
UNITED STATES
/
UNITED STATES OF AMERICA
/
US
/
USA