Polyethylene glycol-conjugated human adrenomedullin as a possible treatment for vascular dementia.
Peptides
; 121: 170133, 2019 11.
Article
en En
| MEDLINE
| ID: mdl-31449828
ABSTRACT
Adrenomedullin (AM) is a multifunctional bioactive peptide. Recent studies have shown that AM has protective effects against ischemic brain damage. We recently prepared a long-acting human AM derivative that was conjugated with a 60â¯kDa polyethylene glycol (PEG-AM), which had an effect similar to that of native AM. In this study, we examined the effect of PEG-AM on four-vessel occlusion model rats, which exhibit vascular dementia. From day 10 to day 14 after surgery, the learning and memory abilities of the rats were examined using a Morris water maze. The rats were treated with a single subcutaneous injection of 1.0 or 10.0â¯nmol/kg of PEG-AM. PEG-AM treatment reduced the escape latency in the hidden platform test. Furthermore, the treatment increased the time spent in the platform quadrant in the probe test. The data showed that PEG-AM injection prevented memory loss and learning disorders in dose-dependent manner. On day 14, the immunoreactive AM concentration in plasma was 9.749⯱â¯2.167â¯pM in the high-dose group (10.0â¯nmol/kg) and 0.334⯱â¯0.073â¯pM in the low-dose group (1.0â¯nmol/kg). However, even in the low-dose group, a significant effect was observed in both tests. The present data indicate that PEG-AM is a possible therapeutic agent for the treatment of ischemic brain injury or vascular dementia.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Vasodilatadores
/
Insuficiencia Vertebrobasilar
/
Lesiones Encefálicas
/
Glicoconjugados
/
Demencia Vascular
/
Daño por Reperfusión
/
Nootrópicos
/
Adrenomedulina
Límite:
Animals
/
Humans
/
Male
Idioma:
En
Revista:
Peptides
Año:
2019
Tipo del documento:
Article