PAR-1, -4, and the mTOR Pathway Following Germinal Matrix Hemorrhage.
Acta Neurochir Suppl
; 121: 213-6, 2016.
Article
en En
| MEDLINE
| ID: mdl-26463951
ABSTRACT
Germinal matrix hemorrhage (GMH) is the most common cause of neurological complications of prematurity and has lasting implications. PAR-1 and PAR-4 receptors are involved with upstream signaling pathways following brain hemorrhage in adult models of stroke, of which the mammalian target of rapamycin (mTOR) is a potential downstream mediator. Therefore, we hypothesized a role for PAR-1, -4/ mTOR signaling following GMH brain injury. Postnatal day 7 Sprague-Dawley rats were subjected to GMH through stereotactic infusion of collagenase into the right ganglionic eminence. Rodents were euthanized at 72 h (short term), or 4 weeks (long term). Short-term mTOR expression was evaluated by Western blot in the context of PAR-1 (SCH-79797) and PAR-4 (P4pal10) inhibition. Pups in the long-term group were administered the selective mTOR inhibitor (rapamycin) with neurobehavioral and brain pathological examinations performed at 4 weeks. Pharmacological PAR-1, -4 antagonism normalized the increased mTOR expression following GMH. Early inhibition of mTOR by rapamycin improved long-term outcomes in rats. Mammalian-TOR signaling plays an important role in brain injury following neonatal GMH, possibly involving upstream PAR-1, -4 mechanisms.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Oligopéptidos
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Pirroles
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Quinazolinas
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Encéfalo
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Trombina
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Receptores de Trombina
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Hemorragias Intracraneales
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Receptor PAR-1
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Serina-Treonina Quinasas TOR
Límite:
Animals
Idioma:
En
Revista:
Acta Neurochir Suppl
Año:
2016
Tipo del documento:
Article
País de afiliación:
Estados Unidos