Calmodulin inhibitor ameliorates cognitive dysfunction via inhibiting nitrosative stress and NLRP3 signaling in mice with bilateral carotid artery stenosis.

ABSTRACT:

Aims

Vascular dementia (VaD) is a heterogeneous brain disorder for which there are no effective approved pharmacological treatments available. We aimed to evaluate the effect of calmodulin inhibitor, DY-9836, and its loaded nanodrug carrier system on cognitive impairment and gain a better understanding of the protective mechanisms in mice with bilateral carotid artery stenosis (BCAS).

Results

DY-9836 (0.5 or 1 mg/kg) or DY-9836 (0.25 mg/kg)-encapsulated polysialic acid-octadecylamine (PSA-ODA) micelles (PSA-ODA/DY) were given to BCAS mice for 4 weeks. Administration of DY-9836 or PSA-ODA/DY reduced escape latency in space exploration and working memory test compared with vehicle group. Vehicle-treated mice showed reduced phospho-CaMKII (Thr286/287) levels in the hippocampus,

SUBMITTER: Wang R 

PROVIDER: S-EPMC6492762 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature