Mannose-binding lectin promotes blood-brain barrier breakdown and exacerbates axonal damage after traumatic brain injury in mice.
Exp Neurol
; 346: 113865, 2021 12.
Article
en En
| MEDLINE
| ID: mdl-34547288
ABSTRACT
Leukocyte infiltration and blood-brain barrier breakdown contribute to secondary brain damage after traumatic brain injury (TBI). TBI induces neuroimmune responses triggering pathogenic complement activation through different pathways, including the lectin pathway. We investigated mechanisms underlying mannose-binding lectin (MBL)-mediated brain damage focusing on neutrophil infiltration and blood-brain barrier breakdown in a TBI mouse model. Wild type mice and MBL-/- null mice were subjected to controlled cortical impact. We studied neutrophil infiltration and regional localization by confocal microscopy 1, 4 and 15 days post-trauma, and investigated neutrophil extracellular trap (NET) formation. By immunofluorescence and/or Western blotting in various brain regions we studied the presence of fibrin(ogen), pentraxin-3, albumin and immunoglobulin G. Finally, we studied neurofilament proteins, synaptophysin, and αII-spectrin, and assessed white matter content in the injured tissue. TBI triggered an acute wave of neutrophil infiltration at day 1 followed by a more discrete persistence of neutrophils in the injured tissue at least until day 15. We detected the presence of NETs and pentraxin-3 in the injured tissue, as well as accumulation of fibrin(ogen), increased blood-brain barrier permeability, and neurofilament, synaptophysin and white matter loss, and calpain-mediated αII spectrin breakdown. MBL-/- mice showed reduced number of Ly6G+ neutrophils 4 days after TBI, lower accumulation of pentraxin-3 and fibrin(ogen) in the injured tissue, reduced global plasma protein extravasation, and better preservation of axonal and white matter integrity. These results show that MBL participates in secondary neutrophil accumulation and blood-brain barrier breakdown, and promotes axonal and white matter damage after TBI in mice.
Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Axones
/
Encéfalo
/
Barrera Hematoencefálica
/
Lectina de Unión a Manosa
/
Lesiones Traumáticas del Encéfalo
Límite:
Animals
Idioma:
En
Revista:
Exp Neurol
Año:
2021
Tipo del documento:
Article
País de afiliación:
España