Open AccessRho Kinase Inhibitor Fasudil Protects against β ‐Amyloid‐Induced Hippocampal Neurodegeneration in Rats
Author(s) -
Song Yun,
Chen Xu,
Wang LiYan,
Gao Wei,
Zhu MeiJia
Publication year - 2013
Publication title -
cns neuroscience and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 69
eISSN - 1755-5949
pISSN - 1755-5930
DOI - 10.1111/cns.12116
Subject(s) - fasudil , neuroprotection , neurodegeneration , neuroinflammation , hippocampal formation , medicine , pharmacology , rho kinase inhibitor , tumor necrosis factor alpha , inflammation , neuroscience , rho associated protein kinase , endocrinology , kinase , chemistry , biology , disease , biochemistry
Summary Background and purpose Alzheimer's disease ( AD ) is a progressive neurodegenerative disorder, and A β ‐induced neuronal damage is the major pathology of AD . There is increasing evidence that neuroinflammation induced by A β is also involved in the pathogenesis of AD . Fasudil is a Rho kinase inhibitor and has been reported to have neuroprotective effects. In this study, the main purpose is to investigate whether fasudil has beneficial effects on cognitive impairment and neuronal toxicity induced by A β . Methods and results In the present study, intracerebroventricular injection of A β 1–42 to rats resulted in marked cognitive impairment, severe neuronal damage, as well as increased IL ‐1 β , tumor necrosis factor alpha ( TNF ‐α) production, and NF ‐κB activation. Administration of fasudil significantly ameliorated the spatial learning and memory impairment, attenuated neuronal loss, and neuronal injury induced by A β 1–42 . In addition, fasudil inhibited IL ‐1 β and TNF ‐α production and NF ‐κB activation in the rat brain. Conclusions Fasudil can protect against A β ‐induced hippocampal neurodegeneration by suppressing inflammatory response, suggesting that fasudil might be a promising agent for the prevention and treatment of inflammation‐related diseases, such as AD .