Recombinant High-Density Lipoprotein Boosts the Therapeutic Efficacy of Mild Hypothermia in Traumatic Brain Injury.
ACS Appl Mater Interfaces
; 15(1): 26-38, 2023 Jan 11.
Article
en En
| MEDLINE
| ID: mdl-35833835
ABSTRACT
Traumatic brain injury (TBI) leads to neuropsychiatric symptoms and increased risk of neurodegenerative disorders. Mild hypothermia is commonly used in patients suffering from severe TBI. However, its effect for long-term protection is limited, mostly because of its insufficient anti-inflammatory and neuroprotective efficacy and restricted treatment duration. Recombinant high-density lipoprotein (rHDL), which possesses anti-inflammatory and antioxidant activity and blood-brain barrier (BBB) permeability, was expected to potentially strengthen the therapeutic effect of mild hypothermia in TBI treatment. To test this hypothesis and optimize the regimen for combination therapy, the efficacy of mild hypothermia plus concurrent or sequential rHDL on oxidative stress, inflammatory reaction, and cell survival in the damaged brain cells was evaluated. It was found that the effect of combining mild hypothermia with concurrent rHDL was modest, as mild hypothermia inhibited the cellular uptake and lesion-site-targeting delivery of rHDL. In contrast, the combination of mild hypothermia with sequential rHDL more powerfully improved the anti-inflammatory and antioxidant activities, promoted nerve cell survival and BBB restoration, and ameliorated neurologic changes, which thus remarkably restored the spatial learning and memory ability of TBI mice. Collectively, these findings suggest that rHDL may serve as a novel nanomedicine for adjunctive therapy of TBI and highlight the importance of timing of combination therapy for optimal treatment outcome.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Lesiones Encefálicas
/
Lesiones Traumáticas del Encéfalo
/
Hipotermia
/
Hipotermia Inducida
Límite:
Animals
Idioma:
En
Revista:
ACS Appl Mater Interfaces
Asunto de la revista:
BIOTECNOLOGIA
/
ENGENHARIA BIOMEDICA
Año:
2023
Tipo del documento:
Article
País de afiliación:
China