Inhibition of cyclooxygenase and EP3 receptor improved long term potentiation in a rat organotypic hippocampal model of repeated blast traumatic brain injury.
Neurochem Int
; 163: 105472, 2023 02.
Article
en En
| MEDLINE
| ID: mdl-36599378
ABSTRACT
Blast-induced traumatic brain injury (bTBI) is a health concern in military service members who are exposed to multiple blasts throughout their training and deployment. Our group has previously reported decreased long term potentiation (LTP) following repeated bTBI in a rat organotypic hippocampal slice culture (OHSC) model. In this study, we investigated changes in inflammatory markers like cyclooxygenase (COX) and tested the efficacy of COX or prostaglandin EP3 receptor (EP3R) inhibitors in attenuating LTP deficits. Expression of COX-2 was increased 48 h following repeated injury, whereas COX-1 expression was unchanged. EP3R expression was upregulated, and cyclic adenosine monophosphate (cAMP) concentration was decreased after repeated blast exposure. Post-traumatic LTP deficits improved after treatment with a COX-1 specific inhibitor, SC-560, a COX-2 specific inhibitor, rofecoxib, a pan-COX inhibitor, ibuprofen, or an EP3R inhibitor, L-798,106. Delayed treatment with ibuprofen and L-798,106 also prevented LTP deficits. These findings suggest that bTBI induced neuroinflammation may be responsible for some functional deficits that we have observed in injured OHSCs. Additionally, COX and EP3R inhibition may be viable therapeutic strategies to reduce neurophysiological deficits after repeated bTBI.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Traumatismos por Explosión
/
Lesiones Traumáticas del Encéfalo
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Neurochem Int
Año:
2023
Tipo del documento:
Article