Rho Kinase Inhibitor Fasudil Protects againstβ-Amyloid-Induced Hippocampal Neurodegeneration in Rats

Abstract

Alzheimer's disease (AD) is a progressive neurodegenerative disorder, and Aβ-induced neuronal damage is the major pathology of AD. There is increasing evidence that neuroinflammation induced by Aβ 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 Aβ. In the present study, intracerebroventricular injection of Aβ1-42 to rats resulted in marked cognitive impairment, severe neuronal damage, as well as increased IL-1β, 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 Aβ1-42 . In addition, fasudil inhibited IL-1β and TNF-α production and NF-κB activation in the rat brain. Fasudil can protect against Aβ-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.