Soluble epoxide hydrolase inhibition alleviated cognitive impairments via NRG1/ErbB4 signaling after chronic cerebral hypoperfusion induced by bilateral carotid artery stenosis in mice.

Soluble epoxide hydrolase inhibition alleviated cognitive impairments via NRG1/ErbB4 signaling after chronic cerebral hypoperfusion induced by bilateral carotid artery stenosis in mice. Brain Res. 2018 Nov 15;1699:89-99 Authors: Hao J, Chen Y, Yao E, Liu X Abstract Cerebral ischemic stroke is associated with a high rate of incidence, prevalence and mortality globally. Carotid artery stenosis, which is mainly caused by atherosclerosis plaque, results in chronic cerebral hypoperfusion and predominantly increases the risk of ischemic stroke. In the present study, we used bilateral common carotid artery stenosis (BCAS) model by placing microcoils of 0.18 mm diameter encompassing both common carotid arteries respectively, to mimic the pathogenesis of carotid artery atherosclerosis and intensively explore the pathology. We found that BCAS injury for 1 month impaired spatial cognitive functions significantly, and inhibited synaptic plasticity, including hippocampal long-term potentiation (LTP) inhibition, dendritic spine density reduction and synaptic associative proteins disorder. BCAS-induced cerebral hypoperfused mice treated with 1-(1-propanoylpiperidin-4-yl)-3-[4-(trifluoromethoxy)phenyl]urea (TPPU), a potent soluble epoxide hydrolase (sEH) inhibitor, exhibited amelioration of cognitive dysfunction and improved synaptic plasticity. The neural protective effects of TPPU on BCAS-induced cerebral hypoperfusion might due to activation ...
Source: Brain Research - Category: Neurology Authors: Tags: Brain Res Source Type: research