Effects of Poly(ADP-Ribose) Polymerase-1 Inhibition in a Neonatal Rodent Model of Hypoxic-Ischemic Injury.
Biomed Res Int
; 2017: 2924848, 2017.
Article
em En
| MEDLINE
| ID: mdl-28698869
ABSTRACT
BACKGROUND:
Hypoxia ischemia (HI) to the developing brain occurs in 1-6 in 1000 live births. Large numbers of survivors have neurological long-term sequelae. However, mechanisms of recovery after HI are not understood and preventive measures or clinical treatments are not effective. Poly(ADP-ribose) polymerase-1 is overactivated in response to ischemia. In neonatal mice HI activates PARP-1 but its role in perinatal brain injury remains uncertain.OBJECTIVE:
Aim of this study was to explore the effect of TES448 (PARP-1-inhibitor) and hypothermia after an ischemic insult. DESIGN ANDMETHODS:
10-day-old Wistar rats underwent HI. TES448 was given 10 min, 3 hrs, and 6 hrs after hypoxia. Hypothermia was started 30 min after HI and brains were dissected at P12. Western blotting and histological staining were used to evaluate for degree of injury.RESULTS:
Protein expression of PARP-1 levels was diminished after TES448 treatment. Cresyl violet and TUNEL staining revealed decreased injury in male rat pups following TES448 and combined treatment. Female rats showed increased numbers of TUNEL-positive cells after combined therapy. TES448 inhibited microglia activation after hypoxic-ischemic injury. A cellular response including NeuN, Olig2, and MBP was not affected by PARP-1-inhibition.CONCLUSIONS:
Inhibition of PARP-1 and hypothermia lead to an alteration of injury but this effect is sexually dimorphic.
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Encéfalo
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Lesões Encefálicas
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Regulação Enzimológica da Expressão Gênica
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Isquemia Encefálica
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Poli(ADP-Ribose) Polimerase-1
Limite:
Animals
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article