Intravenous Immunomodulatory Nanoparticle Treatment for Traumatic Brain Injury.
Ann Neurol
; 87(3): 442-455, 2020 03.
Article
em En
| MEDLINE
| ID: mdl-31925846
ABSTRACT
OBJECTIVE:
There are currently no definitive disease-modifying therapies for traumatic brain injury (TBI). In this study, we present a strong therapeutic candidate for TBI, immunomodulatory nanoparticles (IMPs), which ablate a specific subset of hematogenous monocytes (hMos). We hypothesized that prevention of infiltration of these cells into brain acutely after TBI would attenuate secondary damage and preserve anatomic and neurologic function.METHODS:
IMPs, composed of US Food and Drug Administration-approved 500nm carboxylated-poly(lactic-co-glycolic) acid, were infused intravenously into wild-type C57BL/6 mice following 2 different models of experimental TBI, controlled cortical impact (CCI), and closed head injury (CHI).RESULTS:
IMP administration resulted in remarkable preservation of both tissue and neurological function in both CCI and CHI TBI models in mice. After acute treatment, there was a reduction in the number of immune cells infiltrating into the brain, mitigation of the inflammatory status of the infiltrating cells, improved electrophysiologic visual function, improved long-term motor behavior, reduced edema formation as assessed by magnetic resonance imaging, and reduced lesion volumes on anatomic examination.INTERPRETATION:
Our findings suggest that IMPs are a clinically translatable acute intervention for TBI with a well-defined mechanism of action and beneficial anatomic and physiologic preservation and recovery. Ann Neurol 2020;87442-455.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Lesões Encefálicas Traumáticas
/
Fatores Imunológicos
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article